Molecules 2013, 18,1-x manuscripts; doi:10.3390/molecules180x0000x

molecules ISSN 1420-3049

www.mdpi.com/journal/molecules Review

Medicinal Plants with Antitumor Potential against Lung Cancer

Luara de Sousa Monteiro, Katherine Xavier Bastos, José Maria Barbosa-Filho, Petrônio Filgueiras de Athayde-Filho, Margareth de Fátima Formigo Melo Diniz, and Marianna Vieira Sobral Castello-Branco*,

Department of Pharmaceutical Sciences, Federal University of Paraiba, 58051-900, João Pessoa, PB, Brazil; E-Mails: luaramonteiro@hotmail.com (L.S.M.); katherine_xb@hotmail.com (K.X.B.); jbarbosa@ltf.ufpb.br (J.M.B.-F.); athayde-filho@quimica.ufpb.br (P.F.A.-F.); margareth@ltf.ufpb.br (M.F.F.M.D.)

* Author to whom correspondence should be addressed; E-Mail: mariannavbs@gmail.com (M.V.S.C.B.); Tel.: +55-83- 3216-7003; Fax: +55-83-3216-7364.

Received: / Accepted: /Published:

Abstract: Lung cancer is a disease with a high morbidity and high mortality rates. As a result, it is

often associated with a significant amount of suffering and a general decrease in the quality of life.

Herbal drugs are recognized as one of attractive approaches for lung cancer therapy with little side

effects and are the main sources of new drugs. The aim of this review is to review the medicinal plants

with antitumor potential against lung cancer. The assays were conducted with humans and animals,

and Lewis lung carcinoma was the most used experimental model. Considering all the countries

covered in the study, India, China, Japan, and South Korea were the countries with the highest number

of species with antitumor activity on different experimental models. Of the 47 plants evaluated, 35

demonstrated antitumor activity. This review was based on NAPRALERT data bank, Web of Science

and Chemical Abstracts. This work shows that the natural products from plants continue being a rich

source of herbal medicines or biologically active compounds against cancer.

Keywords: medicinal plants; antitumor activity; lung cancer; review

1. Introduction

OPEN ACCESS

Molecules 2013, 18

2

Cancer is a collection of heterogeneous genetic diseases united by common alterations in multiple

cellular signaling pathways [1]. Different hallmarks are proposed to cancer cells. Evasion of

programmed cell death or apoptosis has been recognized as one of the main alterations that dictate

malignant growth [2]. Furthermore, other hallmarks include self-sufficiency in growth signal,

deregulating cellular energetics, sustained angiogenesis, evasion immune detection, and tissue invasion

and metastasis [1-3]. In addition, have been described two characteristics of cancer that facilitate

acquisition of the hallmarks: genome instability and mutation tumor-promoting inflammation [2].

Coordinated processes such as cell proliferation, differentiation and apoptosis are modified producing

altered cellular phenotype with these specific characteristics [1,2].

According to the World Health Organization (WHO), the cancer are non-communicable diseases

responsible for 63% of deaths worldwide, being characterized as the second cause of death in western

countries [4,5]. Its incidence is strongly affected by demographics aspects, such as population aging,

feeding habits and, in particular, environmental factors such as the incidence of ultra-violet rays. The

International Agency for Research on Cancer (IARC) estimates that there were 12.7 million new

cancer cases in 2008 and is expected by 2030 to grow to 21.4 million [6,7].

Lung cancer is currently the malignant tumor with the highest rate of mortality worldwide, often

because it is not detected until there has been significant progression of the illness, which leads to a

significant reduction in quality of life of the patient [8]. Different factors are classified as possible

causes for lung cancer, including active cigarette smoking; exposure to secondhand cigarette smoke

(passive smoking); pipe and cigar smoking; exposure to indoor and outdoor air pollution; exposure to

radiation; and occupational exposure to agents such as asbestos, nickel, chromium, and arsenic [9].

The most important factor is smoking [10] and the incidence rates of lung cancer are generally higher

among men than among women [11]. The lung cancer is classified into non-small cell lung carcinoma

(NSCLC): squamous cell carcinoma, adenocarcinoma or large cell carcinoma, which represents 80%

of all lung cancer cases, and the remaining cases are small cell lung carcinoma (SCLC) [11,12].

Recently, it was published a new classification that defined ‘‘molecular subtypes’’ of lung cancer

based on specific actionable genetic aberrations [13]. New opportunities for targeted therapy are under

development based on the discovery of multiple molecular mechanisms underlying the development,

progression, and prognosis of lung cancer.

Surgery, chemotherapy, radiation, hormones and immunotherapy are the main cancer treatment

often supplemented by other complementary and alternative therapies. Although chemotherapy is the

method most used, several problems are associated with its use as limited efficacy, toxicity severe and

multi-drug resistant [14].

Molecules 2013, 18

3

Plants have a long history of use in the treatment of cancer and continue to be the main source of

new drugs [15]. Herbal drugs have been recognized as one of attractive approaches for lung cancer

therapy because they have proven to be useful and effective in sensitizing conventional agents,

prolonging survival time, preventing side effects of chemotherapy, and improving quality of life in

lung cancer patients [16]. Recent cohort study with 453 cancer patients revealed that the percentage of

patients using herbal medicines in combination with conventional treatment was as high as 77% [17].

These data demonstrate the importance of natural products as complementary therapy for the treatment

of lung cancer, mainly with the aims of reduction of toxicity, improvement of cancer-related

symptoms, fostering of the immune system, and even direct anti-cancer effects [18].

Many natural products or synthetic analogs are still widely used in clinical, for example, the so-

called vinca alkaloids, vinblastine and vincristine, isolated from the Madagascar periwinkle,

Catharanthus roseus, the paclitaxel (Taxol®), obtained of the leaves of various Taxus species, and the

two clinically-active agents, etoposide and teniposide, which are semisynthetic derivatives of the

natural product epipodophyllotoxin [15]. In addition, other promising agents, natural or synthetic

analogs, are in clinical development phase, including flavopiridol [19] and combretastatin A4 [20].

In the course of our continuing search for bioactive natural plant products, we have published

reviews on crude plant extracts and plant-derived compounds with potential uses [21-38]. Moreover,

our group has also reviewed the medicinal and poisonous plants of Northeast Brazil [39-40], among

others [41-53].

The search was carried out on data banks such as Web of Science, Chemical Abstracts, and

NAPRALERT (acronym for the University of Illinois Natural Products ALERT service). The

references found in the searches were later consulted. For details on the mechanism-based bioassays

utilized for antitumor activity, the original references should be consulted.

2. Results and Discussion

Herbal medicines and phytochemicals can be potent anti-cancer agents for lung cancer treatment

and prevention by regulating multi-molecular targets involved in angiogenesis, metastasis and severe

side effects, only provided quality control and reproducibility issues were solved [16].

In the current review we present medicinal plants, distributed in diverse parts of the world, with

antitumor activity against different lung tumor models. The effectiveness of the medicinal plants

depended on the type of drug studied and the bioassay models. Thus, it was possible to classify the

extracts as active or inactive. In this study, we chose more species referenced in data collected in the

NAPRALERT natural products database and the scientific literature databases ScienceDirect and

PubMed.

Molecules 2013, 18

4

Euphorbiaceae and Fabaceae were the most cited families for antitumor activity against lung tumor

models, respectively. Croton macrostachys, Euphorbia esula, Euphorbia fischeriana and Euphorbia

ingens were the most studied Euphorbiaceae species. All of them showed significant antitumor activity

against lung tumor models. Among the Fabaceae active species were cited Caesalpinia gilliesii, Cassia

garrettiana, and Sophora flavescens.

Eleven mentions were described for the specie Ganoderma lucidum (Ganodermataceae), being

considered the most studied specie for antitumor activity against lung tumor models. One of these

studies showed that an aqueous extract of Ganoderma lucidum, called ‘Ling-Zhi or holy mushroom’ in

Chinese traditional medicine, significantly increased the life span of Lewis lung carcinoma-implanted

syngeneic C57BL/6 mice, when administered intraperitoneally alone or in combination with cytotoxic

antitumor drugs (Adriamycin, fluorouracil, thioguanine, methotrexate, cisplatin) or a synthetic

immunomodulator (Imexon) [54]. In another study, the authors suggest that the antitumor and

antimetastatic activities of the triterpenoid fraction of G. lucidum against Lewis lung carcinoma

(LLC)-implanted might be due to the inhibition of tumor-induced angiogenesis [55].

The species Undaria pinnatifida, Panax ginseng red type, Brucea javanica and Camellia sinensis

were also active against lung tumor models. To Undaria pinnatifida specie, four studies showed

significant activity against Lewis lung carcinoma. Among the four mentions for Panax ginseng red

type, one of the studies showed the antitumor activity of this specie against lung adenoma induced by

different carcinogenic agents.

The Brucea javanica species showed the anti-carcinoma effect against brain metastasis as a

complication of lung cancer. The results of this study showed that the median survival duration (15

months in the test group, 10 months in the control group) and the quality of life of the patients in the

combined group (radiotherapy and intravenous injection of 10% Brucea javanica emulsion) was much

better than in the radiotherapy alone (control) group. The results suggest the Brucea javanica emulsion

exhibits a synergic action with the radiotherapy in the treatment of brain metastasis as a complication

of lung cancer [56]. Another study with this species showed that the preoperative intravenous emulsion

of 10% Brucea javanica oil emulsion may improve surgical treatment of non-small cell lung cancer

[57].

Considering all the countries covered in the study, India, China, Japan, and South Korea were the

countries with the highest number of species with antitumor activity on different experimental models.

The most used cellular model for investigation of antitumor activity against lung cancer was the

Lewis lung carcinoma. Of the 58 studies that show this cell line being used as an experimental model,

44 showed its sensibility to the samples tested. This shows that this cell line is the most used model

Molecules 2013, 18

5

worldwide to evaluate the antitumor activity in lung cancer cells. Other models cited in few studies

include Small cell lung, Lung cancer and adenomas.

3. Conclusions

Several countries study medicinal plants with antitumor potential, including against lung cancer.

Many species are active in different experimental models. This shows that the natural products from

plants continue being a rich source of herbal medicines or biologically active compounds. There is a

need for further studies on the standardization or chemical characterization of the extracts used. With

respect to pharmacological studies, the most of them it was performed on mice. However studies with

human were also observed for different species of plants. Therefore, new research findings could lead

to greater safety and benefits to people contributing to a better access to health care and thereby a

better quality of life of patients with lung cancer.

Acknowledgments

The authors thank the University of Illinois at Chicago, USA for the use of the NAPRALERT

database for this study and A. Leyva for the English revision of the manuscript. Thanks are in order

also for the financial support provided by CAPES/CNPq/PRONEX-FAPESQ.

Conflicts of Interest

The authors declare no conflict of interest.

Table 1. Medicinal plants and other organisms with antitumor potential against lung cancer.

Family and botanical name

Origin

Part used

Extract

Model

Mammal tested

Result

Reference

AGAVACEAE Yucca aloifolia

USA

Flowers

MeOH Ext

Ca-lewis lung

Mouse

Active

[58]

ALARIACEAE

Undaria pinnatifida

Hawaii

Commercial sample of thallus pacific

Type ext not stated

Ca-lewis lung

Mouse

Active

[59]

Hawaii

Commercial sample of thallus pacific

H2O- Insoluble Extract

Ca-lewis lung

Mouse

Active

[59]

Japan

Commercial sample of thallus pacific

H2O Ext

Ca-lewis lung

Mouse

Active

[60]

Japan

Dried thallus pacific

Polysaccharide fraction

Ca-lewis lung

Mouse

Active

[61]

ANACARDIACEAE

Semecarpus anacardium

India

Dried fruit

CHCl3 Ext

Ca-lewis lung

Mouse

Inactive

[62]

APIDAE

Apis mellifera

Croatia

Fresh venom

Venom

Decreased number of lung

metastases

Mouse

Active

[63]

Molecules 2013, 18

2

APOCYNACEAE

Ervatamia heyneana

India

Leaf

MeOH Ext

Ca-lewis lung

Mouse

Inactive

[64]

ARALIACEAE

Eleutherococcus senticosus

USSR

Root

EtOH (16%) Ext

Chem. induced tumor

Mouse

Active

[65]

Panax ginseng

South Korea

Dried root

H2O Ext

Mice exposed

to benzopyrene Male

mouse Active

[66]

South Korea

Dried root

H2O Ext

Aflatoxin-induced

lung adenoma Mouse

Active

[67]

South Korea

Dried root

H2O Ext

Fluorenyl-induced Lung adenoma

Mouse

Inactive

[67]

South Korea

Dried root

H2O Ext

DMBA-induced lung adenoma

Mouse

Inactive

[67]

South Korea

Dried root

H2O Ext

Urethane-induced lung adenoma

Mouse

Active

[67]

ARECACEAE

Calamus rotang

India

Aerial parts

EtOH-H2O (50%) Ext

Ca-lewis lung

Mouse

Active

[68]

Molecules 2013, 18

3

ASTERACEAE

Tagetes minuta

Ethiopia

Aerial parts

H2O Ext

Ca-lewis lung

Mouse

Active

[69]

CARCHARHINIDAE

Carcharhinus plumbeus

USA

Serum chesapeake bay

-

Ca-lewis lung

Male mouse

Active

[70]

CELASTRACEAE

Maytenus serrata

Ethiopia

Fruit

EtOH (95%) Ext

Ca-lewis lung

Mouse

Active

[71]

Ethiopia

Stemwood

EtOH (95%) Ext

Ca-lewis lung

Mouse

Active

[71]

Ethiopia

Root

EtOH (95%) Ext

Ca-lewis lung

Mouse

Active

[71]

Kenia

Root

EtOH (95%) Ext

Ca-lewis lung

Mouse

Active

[71]

Kenia

Stemwood

EtOH (95%) Ext

Ca-lewis lung

Mouse

Active

[71]

Molecules 2013, 18

4

CHLORELLACEAE

Chlorella vulgaris

Pacific (Japan)

Dried cells

Chromatographic fraction

Ca-lung-3LL

Female mouse

Active

[72]

CLADONIACEAE

Cladonia leptoclada

New Zealand

Thallus

EtOH-H2O (1:1) Ext

Ca-lewis lung

Mouse

Active

[73]

EUPHORBIACEAE

Croton macrostachys

Ethiopia

Fruit

EtOH (95%) Ext

Ca-lewis lung

Mouse

Active

[74]

Ethiopia

Fruit

EtOH (95%) Ext

Ca-lewis lung

Mouse

Active

[75]

Euphorbia esula

USA

Aerial parts

EtOH (95%) Ext

Ca-lewis lung

Mouse

Inactive

[76]

USA

Entire plant

EtOH (95%) Ext

Ca-lewis lung

Mouse

Active

[77]

Euphorbia fischeriana

China

Dried entire plant

EtOH (95%) Ext

Ca-lewis lung

Mouse

Active

[78]

Euphorbia ingens

South Africa

Fresh stem

EtOH-H2O (1:1) Ext

Ca-lewis lung

Mouse

Inactive

[79]

Jatropha gossypiifolia

Costa Rica

Root

H2O Ext

Ca-Lewis lung

Mouse

Inactive

[80]

Costa Rica

Root

EtOH (95%) Ext

Ca-Lewis lung

Mouse

Inactive

[81]

Molecules 2013, 18

5

FABACEAE

Caesalpinia gilliesii USA Dried fruit H2O Ext Ca-lewis lung Mouse Active [82]

Cassia garrettiana Thailand Dried heartwood MeOH Ext Ca-lewis lung Mouse/ip Active [83]

Thailand Dried heartwood MeOH Ext Ca-lewis lung Mouse/ig Active [84]

Sophora flavescens

China

Dried root

Type ext not stated

Ca-lewis lung

Mouse

Active

[85]

Sutherlandia frutescens

South Africa

Fresh flowers

EtOH-H2O (1:1) Ext

Ca-lewis lung

Mouse

Inactive

[86]

GANODERMATACEAE

Ganoderma lucidum Taiwan Dried fruitbody H2O Ext Ca-lewis lung Mouse Active

[87]

Taiwan Dried fruitbody EtOH (95%) Ext Ca-lewis lung Mouse Active

[87]

Taiwan

Dried fruitbody

H2O Ext in

combination with adriamycin

Ca-lewis lung

Mouse

Active

[87]

Taiwan

Dried fruitbody

H2O Ext in combination with

cisplatin

Ca-lewis lung

Mouse

Active

[87]

Molecules 2013, 18

6

Taiwan

Dried Fruitbody

H2O Ext in combination with

fluorouracil

Ca-lewis lung

Mouse

Active

[87]

Taiwan

Dried fruitbody

H2O Ext in

combination with methotrexate

Ca-lewis lung

Mouse

Active

[87]

Taiwan

Dried fruitbody

H2O Ext in combination with

imexon

Ca-lewis lung

Mouse

Active

[87]

Taiwan

Dried fruitbody

H2O Ext in combination with

thioguanine

Ca-lewis lung

Mouse

Active

[87]

Taiwan

Dried mycelium

Hot H2O Ext

Ca-lewis lung

Mouse

Active

[88]

South Korea

Mycelium

Hot H2O Ext

Ca-lewis lung

Mouse

Active

[89]

Japan

Dried fruitbody

H2O Ext

Ca-lewis lung

Mouse

Active

[90]

GERANIACEAE

Pelargonium graveolens

China

Dried root

Type Ext not stated

Ca-lewis lung

Mouse

Active

[85]

Molecules 2013, 18

7

HYMENOCHAETACEAE

Phellinus linteus South Korea Mycelium Polysaccharide fraction

Cancer cell line NCI-H23 Mouse Active [91]

LILIACEAE Allium sativum

Japan

Aged bulb

Aged garlic extract

used

Sarcoma-180 and LL/2 lung

carcinoma cells

Mouse

Active

[92, 93]

LORANTHACEAE

Viscum album

Germany

Dried aerial parts

H2O soluble fraction

Ca-lewis lung

Female mouse

Inactive

[94]

England

Commercial sample of leaf + stem

Type ext not stated

Small cell lung

Human adult

Active

[95]

Switzerland

Commercial sample of entire plant

H2O Ext

Ca-lewis lung

Mouse

Active

[96]

MALVACEAE

Hespesia populnea India Fruit EtOH-H2O (1:1) Ext Ca-lewis lung Mouse Active [68] Hibicus syriacus

Taiwan

Dried rootbark

Acetone Ext

Ca-human-lung

Mouse

Inactive

[97]

Molecules 2013, 18

8

MELASTOMATACEAE

Memecylon umbellatum

India

Leaf

EtOH-H2O (1:1) Ext

Ca-lewis lung

Mouse

Inactive

[68]

NYCTAGINACEAE

Mirabilis multiflora USA Root H2O Ext Ca-lewis lung Mouse Inactive [98]

NYSSACEAE

Nyssa sylvatica Not stated Stembark H2O Ext Ca-lewis lung Mouse Inactive [99]

OCHNACEAE

Lophira lanceolata Nigeria Rootbark EtOH-H2O (1:1) Ext Ca-lewis lung Mouse Inactive [100]

OSCILLATORIACEAE

Oscillatoria acutissima strain B.1 Hawaii Freeze-dried organism Type ext not stated Ca-lewis lung Mouse Inactive [101]

PAPAVERACEAE

Chelidonium majus

Austria

Dried entire plant

Alkaloid fraction

Lung cancer

Human adult

Active

[102]

Molecules 2013, 18

9

PECTINIDAE

Patinopecten yessoensis

Pacific (Japan)

Fresh organism

Polysaccharide fraction

Cells-human-embryonic-lung

Mouse

Inactive

[103]

RANUNCULACEAE

Nigella sativa India Seed EtOH-H2O (50%) Ext Ca-lewis lung Mouse Active [68]

Singapore

Commercial sample

of seed Chromatographic

fraction Ca-lewis lung

Mouse

Active

[104]

RUBIACEAE Morinda citrifolia

Hawaii

Dried fruit juice

EtOH insoluble fraction

Ca-lewis lung

Mouse

Active

[105]

RHIZOPHORACEAE

Bruguiera sexangula

Papua-New Guinea

Stembark

EtOH (95%) Ext

Ca-lewis lung

Mouse

Active

[106]

SCHISANDRACEAE

Schisandra propinqua

China

Dried root + Stem

Hot H2O Ext

Ca-human-lung

Human adult

Active

[107]

Molecules 2013, 18

10

SIMAROUBACEAE

Brucea javanica

China

Dried part not specified

Type ext not stated

Lung cancer

Human adult

Active

[108]

China

Seed

Seed oil

Squamous carcinoma and

adenocarcinoma

Human adult

Active

[109]

China

Seed

Seed oil

The extract showed a

therapeutic effect for lung cancers

Human adult

Active

[110]

China

Seed

Fixed oil

Patients with lung cancer

Human adult

Active

[111]

SOLANACEAE

Withania somnifera

India

Dried root

EtOH (95%) Ext

Lung adenomas

Mouse Male

Active

[112]

India

Dried entire plant

EtOH (95%) Ext

Lung adenomas

Mouse

Active

[113]

SQUALIDAE

Squalus acanthias

Not stated

Cartilage

H2O Ext

Ca-lewis lung

Mouse

Active

[114]

Molecules 2013, 18

11

THEACEAE

Camellia sinensis

China

Dried leaf

Polyphenolic fraction

Lung cancer

Female mouse

Active

[115]

China

Green leaf

Tea

Lung cancer

Human adult

Active

[116]

China

Black leaf

Leaves

Reduced tumor multiplicity and volume in nnk treated mice

Female mouse

Active

[117]

TRICHOLOMATACEAE

Hypsizigus marmoreus Japan Dried fruit H2O Ext

Ca-lewis lung

Mouse Active [118]

Lentinus edodes

Japan

Dried fruit body

H2O Ext

Ca-lewis lung Mouse

Active

[119]

VIOLACEAE

Viola odorata

South Africa

Fresh leaf

EtOH-H2O (1:1) Ext

Ca-lewis lung Mouse

Inactive

[79]

References

1. Luo, J.; Solimini, N.L.; Elledge, S.J. Principles of cancer therapy: Oncogene and non-oncogene addiction. Cell 2009, 136, 823-837.

2. Hanahan, D.; Weinberg, R.A. Hallmarks of cancer: The next generation. Cell 2011, 144, 646-674.

3. Hanahan, D.; Weinberg, RA. The hallmarks of cancer. Cell 2000, 100, 57-70. 4. Kashfi, K. Dysfunctional cell signaling dynamics in oncology: Diagnostic, prognostic and

treatment opportunities. Biochem. Pharmacol. 2013, 85, 595-596. 5. Alwan, A.; Maclean, D.R.; Riley, L.M.; d'Espaignet, E.T.; Mathers; C.D.; Stevens, G.A.;

Bettcher D. Monitoring and surveillance of chronic non-communicable diseases: progress and capacity in high-burden countries. Lancet 2010, 376, 1861-1868.

6. Ferlay, J.; Parkin, D.M.; Steliarova-Foucher, E. Estimates of cancer incidence and mortality in Europe in 2008. Eur. J. Cancer 2010, 46, 765-781.

7. IARC. Cancer incidence and mortality worldwide. Cancer base. International Agency for Research on Cancer 2011.

8. Ford, D.W.; Koch, K. A.; Ray, D.E.; Selecky, P.A. Palliative and end-of-life care in lung cancer. Chest 2013, 143, (5 Suppl), e498S-512S.

9. Alberg, A.J.; Brock, M.V.; Ford, J.G.; Samet, J.M.; Spivack, S.D. Diagnosis and Management of lung cancer, 3rd ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2013, 143, 1-29.

10. Rom, W.N.; Hay, J.G.; Lee, T.C.; Jiang, Y.; Tchou-Wong, K.M. Molecular and genetic aspects of lung cancer. Am. J. Respir. Crit. Care Med. 2000, 16, 1355-1367.

11. Duarte, R.L.M.; Paschoal, M.E.M. Marcadores moleculares no câncer de pulmão: papel prognóstico e sua relação com o tabagismo. J. Braz. Pneumol. 2005, 32, 56-65.

12. Jemal, A.; Murray, T.; Ward, E.; Samuels, A.; Tiwari, R.C.; Ghafoor, A.; Feuer, E.J.; Thun, M.J. Cancer statistics, 2005. Cancer J. Clin. 2005, 55, 10-30.

13. West, L.; Vidwans, S.J.; Campbell, N.P.; Shrager, J.; Simon, G.R.; Bueno, R.; Dennis, P.A.; Otterson, G.A.; Salgia, R. A novel classification of lung cancer into molecular subtypes. Plos One 2012, 7, 1-11.

14. Tan, W; Lu, J; Huang, M; Li, Y; Chen, M; Wu, G.; Gong, J.; Zhong, Z.; Xu, Z.; Dang, Y.; Guo, J.; Chen, X.; Wang, Y. Anti-cancer natural products isolated from chinese medicinal herbs. Chin. Med. 2011, 6, 1-15.

15. Cragg, G.M.; Newman, D.J. Natural products: A continuing source of novel drug leads. Biochim. Biophys. Acta 2013, 1830, 3670-3695.

16. Jeong, S.J.; Koh, W.; Kim, B.; Kim, S.H. Are there new therapeutic options for treating lung cancer based on herbal medicines and their metabolites? J. Ethnopharmacol. 2011, 138, 652-661.

17. Richardson, M.A; White, J.D. Complementary/alternative medicine and cancer research. A national initiative. Cancer Pract. 2000, 8, 45-48

18. Gerber, B.; Scholz, C.; Reimer, T.; Briese, V.; Janni, W. Complementary and alternative therapeutic approaches in patients with early breast cancer: a systematic review. Breast Cancer Res. Treat. 2006, 95, 199-209.

Molecules 2013, 18

2

19. Sedlacek, H.H. Mechanisms of action of flavopiridol. Crit. Rev. Oncol. Hematol. 2001, 38, 139–170.

20. Kapoor, S. Combretastatin A4 and its emerging antineoplastic effects. Surgery 2013, 153, 881. 21. Moura, M.D.; Torres, A.R.; Oliveira, R.A.G.; Diniz, M.F.F.M.; Barbosa-Filho, J.M. Natural

products as inhibitors of models of mammary neoplasia. Br. J. Phytother. 2001, 5, 124-145. 22. Moura, M.D.; Silva, J.S.; Oliveira, R.A.G.; Diniz, M.F.F.M.; Barbosa-Filho, J.M. Natural

products reported as potential inhibitors of uterine cervical neoplasia. Acta Farm. Bonaer. 2002, 21, 67-74.

23. Silva, J.S.; Moura, M.D.; Oliveira, R.A.G.; Diniz, M.F.F.; Barbosa-Filho, J.M. Natural product inhibitors of ovarian neoplasia. Phytomedicine 2003, 10, 221-232.

24. Honório Júnior, J.E.R.; Soares, P.M.; Melo, C.L.; Arruda Filho, A.C.V.; Sena Filho, J.G.; Barbosa Filho, J.M.; Sousa, F.C.F.; Fonteles, M.M.F.; Leal, L.K.A.; Queiroz, M.G.R.; Vasconcelos, S.M.M.. Atividade farmacológica da monocrotalina isolada de plantas do gênero Crotalaria. Rev. Bras. Farmacogn. 2010, 20, 453-458.

25. Almeida, R.N.; Navarro, D.S.; Barbosa-Filho, J.M. Plants with central analgesic activity. Phytomedicine 2001, 8, 310-322.

26. Falcão, H.S.; Leite, J.A.; Barbosa-Filho, J.M.; Athayde-Filho, P.F.; Chaves, M.C.O.; Moura, M.D.; Ferreira, A.L.; Almeida, A.B.A.; Souza-Brito, A.R.M.; Diniz, M.F.F.M.; Batista, L.M. Gastric and duodenal antiulcer activity of alkaloids: A review. Molecules 2008, 13, 3198-3223.

27. Jesus, N.Z.T.; Falcão, H.S.; Gomes, I.F.; Leite, T.J.A.; Lima, G.R.M.; Barbosa-Filho, J.M.; Tavares, J.F.; Silva, M.S.; Athayde-Filho, P.F.; Batista, L.M. Tannins, peptic ulcers and related mechanisms. Int. J. Mol. Sci. 2012, 13, 3203-3228.

28. Rocha, L.G.; Almeida, J.R.G.S.; Macedo, R.O.; Barbosa-Filho, J.M. A review of natural products with antileishmanial activity. Phytomedicine 2005, 12, 514-535.

29. Barbosa-Filho, J.M.; Vasconcelos, T.H.C.; Alencar, A.A.; Batista, L.M.; Oliveira, R.A.G.; Guedes, D.N.; Falcão, H.S.; Moura, M.D.; Diniz, M.F.F.M.; Modesto-Filho, J. Plants and their active constituents from South, Central, and North America with hypoglycemic activity. Rev. Bras. Farmacogn. 2005, 15, 392-413.

30. Falcão, H.S.; Lima, I.O.; Santos, V.L.; Dantas, H.F.; Diniz, M.F.F.M.; Barbosa-Filho, J.M.;Batista, L.M. Review of the plants with anti-inflammatory activity studied in Brazil. Rev. Bras. Farmacogn. 2005, 15, 381-391.

31. Lima, G.R.M.; Montenegro, C.A.; Almeida, C.L.F.; Athayde-Filho, P.F.; Barbosa-Filho, J.M.; Batista, L.M. Database survey of anti-inflammatory plants in South America: A review. Int. J. Mol. Sci. 2011, 12, 2692-2749.

32. Barbosa-Filho, J.M.; Medeiros, K.C.P.; Diniz, M.F.F.M.; Batista, L.M.; Athayde-Filho, P.F.; Silva, M.S.; Cunha, E.V.L.; Almeida, J.R.G.S.; Quintans-Júnior, L.J. Natural products inhibitorsof the enzyme acetylcholinesterase. Rev. Bras. Farmacogn. 2006, 16, 258-285.

33. Barbosa-Filho, J.M.; Martins, V.K.M.; Rabelo, L.A.; Moura, M.D.; Silva, M.S.; Cunha, E.V.L.; Souza, M.F.V.; Almeida, R.N.; Medeiros, I.A. Natural products inhibitors of the angiotensin onverting enzyme (ACE). A review between 1980-2000. Rev. Bras. Farmacogn. 2006, 16, 421-446.

Molecules 2013, 18

3

34. Amaral, F.M.M.; Ribeiro, M.N.S.; Barbosa-Filho, J.M.; Reis, A.S.; Nascimento, F.R.F.;Macedo, R.O. Plants and chemical constituents with giardicidal activity. Rev. Bras. Farmacogn. 2006, 16, 696-720.

35. Barbosa-Filho, J.M.; Nascimento-Júnior, F.A.; Tomaz, A.C.A.; Athayde-Filho, P.F.; Silva, M.S.; Cunha, E.V.L.; Souza, M.F.V.; Batista, L.M.; Diniz, M.F.F.M. Natural products with antileprotic activity. Rev. Bras. Farmacogn. 2007, 17, 141-148.

36. Falcão, H.S.; Mariath, I.R.; Diniz, M.F.F.M.; Batista, L.M.; Barbosa-Filho, J.M. Plants of the American continent with antiulcer activity. Phytomedicine 2008, 15, 132-146.

37. Mota, K.S.L.; Dias, G.E.N.; Pinto, M.E.F.; Luiz-Ferreira, A.; Souza-Brito, A.R.M.; Hiruma-Lima, C.A.; Barbosa-Filho, J.M.; Batista, L.M. Flavonoids with gastroprotective activity. Molecules 2009, 14, 979-1012.

38. Souto, A.L.; Tavares, J.F.; Silva, M.S.; Diniz, M.F.F.M.; Athayde-Filho, P.F.; Barbosa Filho, J.M. Anti-inflammatory activity of alkaloids: an update from 2000 to 2010. Molecules 2011, 16, 8515-8534.

39. Agra, M.F.; Freitas, P.F.; Barbosa-Filho, J.M. Synopsis of the plants known as medicinal and poisonous in Northeast of Brazil. Rev. Bras. Farmacogn. 2007, 17, 114-140.

40. Agra, M.F.; Silva, K.N.; Basílio, I.J.L.D.; Freitas, P.F.; Barbosa-Filho, J.M. Survey of medicinal plants used in the region Northeast of Brazil. Rev. Bras. Farmacogn. 2008, 18, 472-508.

41. Silva, F.L.; Fischer, D.C.H.; Tavares, J.F.; Silva, M.S.; Athayde-Filho, P.F.; Barbosa-Filho, J.M. Compilation of secondary metabolites from Bidens pilosa L. Molecules 2011, 16, 1070-1102.

42. Quintans Júnior, L.J.; Almeida, J.R.G.S.; Lima, J.T.; Nunes, X.P.; Siqueira, J.S.; Oliveira, L.E.G.; Almeida, R.N.; Athayde-Filho, P.F.; Barbosa-Filho, J.M. Plants with anticonvulsant properties-A review. Rev. Bras. Farmacogn. 2008, 18, 798-819.

43. Sousa, F.C.F.; Melo, C.T.V.; Citó, M.C.O.; Félix, F.H.C.; Vasconcelos, S.M.M.; Fonteles, M.M.F.; Barbosa Filho, J.M.; Viana, G.S.B. Plantas medicinais e seus constituintes bioativos: Uma revisão da bioatividade e potenciais benefícios nos distúrbios da ansiedade em modelos animais. Rev. Bras. Farmacogn. 2008, 18, 642-654.

44. Ribeiro Filho, J.; Falcão, H.S.; Batista, L.M.; Barbosa Filho, J.M.; Piuvezam, M.R. Effects of plant extracts on HIV-1 protease. Curr. HIV Res. 2010, 8, 531-544.

45. Barbosa-Filho, J.M.; Alencar, A.A.; Nunes, X.P.; Tomaz, A.C.A.; Sena-Filho, J.G.; Athayde-Filho, P.F.; Silva, M.S.; Souza, M.F.V.; da-Cunha, E.V.L. Sources of alpha-, beta-, gamma-, delta- and epsilon-carotenes: A twentieth century review. Rev. Bras. Farmacogn. 2008, 18, 135-154.

46. Alves, J.S.; Castro, J.C.M.; Freire, M.O.; da-Cunha, E.V.L.; Barbosa-Filho, J.M.; Silva, M.S. Complete assignment of the 1H and 13C spectra of four triterpenes of the ursane, artane, lupane and friedelane groups. Magn. Reson. Chem. 2000, 38, 201-206.

47. Sena Filho, J.G.; Duringer, J.; Maia, G.L.A.; Tavares, J.F.; Xavier, H.S.; Silva, M.S.; Cunha, E.V.L.; Barbosa-Filho, J.M. Ecdysteroids from Vitex species: Distribution and compilation of their 13C-NMR spectral data. Chem. Biodivers. 2008, 5, 707-713.

Molecules 2013, 18

4

48. Oliveira, S.L.; Silva, M.S.; Tavares, J.F.; Sena-Filho, J.G.; Lucena, H.F.S.; Romero, M.A.V.; Barbosa-Filho, J.M. Tropane alkaloids from genus Erythroxylum: Distribution and compilation of 13C-NMR spectral data. Chem. Biodivers. 2010, 7, 302-326.

49. Vasconcelos, S.M.M.; Honório-Júnior, J.E.R.; Abreu, R.N.D.C.; Silva, M.C.C.; Barbosa-Filho, J.M.; Lobato, R.F.G. Pharmacologic Study of Some Plant Species from the Brazilian Northeast: Calotropis procera, Agava sisalana, Solanum paludosum, Dioscorea cayenensis and Crotalaria retusa. In Medicinal Plants: Classification, Biosynthesis and Pharmacology; Varela, A., Jasiah Ibañez, J., Eds.; Nova Science Publishers, Inc.: Hauppauge, NY, USA, 2009; Volume 4, pp. 189-202.

50. Vasconcelos, S.M.M.; Pereira, E.C.; Chaves, E.M.C.; Lobato, R.F.G.; Barbosa-Filho, J.M.; Patrocínio, M.C.A. Pharmacologic study of Amburana cearensis and Aniba genus. In Recent Progress in Medicinal Plants. Drug Plant IV; Singh, V.K., Govil, J.N., Eds.; Studium Press LLC:Houston, TX, USA, 2010; Volume 30, pp. 51-64.

51. Almeida, C.L.F.; Falcão, H.S.; Lima, G.R.M.; Montenegro, C.A.; Lira, N.S.; Athayde-Filho, P.F.; Rodrigues, L.C.; Souza, M.F.V.; Barbosa-Filho, J.M.; Batista, L.M. Bioactivities from marine algae of the genus Gracilaria. Int. J. Mol. Sci. 2011, 12, 4550-4573.

52. Barbosa-Filho, J.M.; Sette, I.M.F.; Cunha, E.V.L.; Guedes, D.N.; Silva, M.S. Protoberberine alkaloids. In The Alkaloids, Cordell, G.A., Ed.; Elsevier: Amsterdam, The Netherlands, 2005; Volume 62, pp. 1-75.

53. Conserva, L.M.; Pereira, C.A.B.; Barbosa-Filho, J.M. Alkaloids of the Hernandiaceae: Occurrence and a compilation of their biological activities. In The Alkaloids, Cordell, G.A., Ed.; Elsevier: Amsterdam, the Netherlands, 2005; Volume 62, pp. 175-243.

54. Furusawa, E.; Chou, S.C.; Furusawa, S.; Hirazumi, A.; Dang, Y. Antitumour activity of Ganoderma lucidum, an edible mushroom, on intraperitoneally implanted lewis lung carcinoma in synergenic mice. Phytother. Res. 1992, 6, 300-304.

55. Kimura, Y.; Taniguchi, M.; Baba, K. Antitumor and antimetastatic effects on liver of triterpenoid fractions of Ganoderma lucidum: mechanism of action and isolation of an active substance. Anticancer Res. 2002, 22, 3309-3318.

56. Wang, Z.Q.; Chen, Y.M.; Jin, G.W.; Lin, S.S. combined therapy of brain metastasis in lung cancer. Chin. J. Integ. Trad. West Med. 1995, 1, 36-38.

57. Wu, S.C. Preoperative intravenous drip of an anti-tumor Chinese herb preparation, Brucea javanica oil emulsion (Ya Dan Zi Emulsion) for lung cancer. Shang-Hai I Hsueh 1991, 14, 273-275.

58. Sokoloff, B. The oncostatic and oncolytic factors present in certain plants. Oncology 1968, 22, 49.

59. Furusawa, E.; Furusawa, S. Anticancer activity of a natural prodict, viva-natural, extracted from Undaria pinnantifida on intraperitoneally implanted lewis lung carcinoma. Oncology 1985, 42, 364-369.

60. Furusawa, E.; Furusawa, S. Anticancer potential of viva-natural, a dietary seaweed extract, on lewis lung carcinoma in comparison with chemical immunomodulators and on cyclosporine-accelerated akr leukemia. Oncology 1989, 46, 343-349.

Molecules 2013, 18

5

61. Furusawa, E.; Furusawa, S. Antitumor potential of low-dose chemotherapy manifested in combination with immunotherapy of viva-natural, a dietary seaweed extract, on lewis lung carcinoma. Cancer Lett. 1990, 50, 71-78.

62. Chitnis, M.P.; Bhatia, K.G.; Phatak, M.K.; Rao, K.V.K. Anti-tumor activity of the extract of Semecarpus anacardium L. nuts in experimental tumour models. Indian J. Exp. Biol. 1980, 18, 6-8.

63. Curic, S.; Tadic, Z.; Valpotic, I.; Sulimanovic, D.; Basic, I. The effect of bee venom on tumor growth and metastasis formation of mammary carcinoma in CBA mice. Veterinarski Arhiv 1992, 62, S31-S35.

64. Chitnis, M.P; Bhatia, K.G.; Phatak, M.K. Anti-tumor activity of the methanol extract Ervatamia heyneana. Indian J. Exp. Biol. 1979, 17, 212.

65. Djioev, F.K. Influence of extract of eleutherococcus on arising of urethane induced lung adenomas in mice. Vopr. Onkol. 1965, 11, 51.

66. Yun, Y.S.; Lee, Y.S.; Jo, S.K.; Jung, I.S. Inhibition of autochthonous tumor by ethanol insoluble fraction from Panax ginseng as an immunomodulator. Planta Med. 1993, 59, 521-524.

67. Yun, T.K.; Yun, Y.S.; Han, I.W. An experimental study on tumor inhibitory effect of red ginseng in mice and rats exposed to various chemical carcinogens. Proc. 3rd Int. Ginseng Symp. Seoul, South Korea 1980, 87-113.

68. Dhar, M.L.; Dhar, M.M.; Dhawan, B.N.; Mehrotra, B.N.; Ray, C. Screening of Indian plants for biological activity: part I. Indian J. Exp. Biol. 1968, 6, 232-247.

69. Ickes, G.R.; Fong, H.H.S.; Schiff Jr, P.L.; Perdue Jr, R.E.; Farnsworth, N.R. Antitumor activity and preliminary phytochemical examination of Tagetes minuta (Compositae). J. Pharm. Sci. 1973, 62, 1009-1011.

70. Snodgrass, M.J.; Burke, J.D.; Meetz, G.D. Inhibitory effect of shark serum on the lewis lung carcinoma. J. Nat. Cancer Inst. 1976, 56, 981-983.

71. Kupchan, S.M.; Komoda, Y.; Court, W.A.; Thomas, G.J.; Smith, R.M.; Karim, A.; Gilmore, C.J.; Haltiwanger, R.C.; Bryan, R.F. Tumor inhibitors. LXXIII. Maytansine, a novel antileukemic ansa macrolide from Maytenus ovatus. J. Amer. Chem. Soc. 1972, 94, 1354-1356.

72. Noda, K.; Ohno, N.; Tanaka, K.; Okuda, M.; Yadomae, T.; Nomoto, K.; Shoyama, Y. A new type of biological response modifier from Chlorella vulgaris which needs protein moiety to show an antitumour activity. Phytother. Res. 1998, 12, 309-319.

73. Kupchan, S.M.; Kopperman, H.L. L-Usnic Acid: Tumor inhibitor isolated from lichens. Experientia 1975, 31, 625.

74. Kupchan, S.M.; Hemingway, R.J.; Coggon, P.; Mc Phail, A.T.; Sim, G.A. Crotepoxide, a novel cyclohexane diepoxide tumor inhibitor from Croton macrostachys. J. Amer. Chem. Soc. 1968, 90, 2982.

75. Kupchan, S.M.; Hemingway, R.J.; Smith, R.M. Tumor Inhibitors. XLV. Crotepoxide, a novel cyclohexane diepoxide tumor inhibitor from Croton macrostachys. J. Org. Chem. 1969, 34, 3898.

Molecules 2013, 18

6

76. Farnsworth, N.R.; Wagner, H.; Horhammer, L.; Horhammer, H.P.; Fong, H.H.S. Euphorbia esula (Euphorbiaceae). I. Preliminary phytochemical and biological evaluation. J. Pharm. Sci. 1968, 57, 933-940.

77. Kupchan, S.M.; Uchida, I.; Branfman, A.R.; Dailey Jr, R.G.; Fei, B.Y. Antileukemic principles isolated from Euphorbiaceae plants. Science 1976, 191, 571-572.

78. Shentu, J.; Wei, P.; Wang, A; Et Al. A study of the antitumor effect of Euphorbia fischeriana steud on mice with induced tumor. Chin. J. Integ. Trad. West Med. 1984, 4, 46-47.

79. Charlson, A.J. Antineoplastic constituents of some southern African plants. J. Ethnopharmacol. 1980, 2, 323-335.

80. Kupchan, S.M.; Sigel, C.W.; Matz, M.J.; Saenz Renauld, J.A.; Haltiwanger, R.C.; Bryan, R.F. Jatrophone a novel macrocyclic diterpenoid tumor inhibitor from Jatropha gossypiifolia. J. Amer. Chem. Soc. 1970, 92, 4476.

81. Kupchan, S.M.; Sigel, C.W.; Matz, M.J.; Saenz Renauld, J.A.; Haltiwanger, R.C.; Bryan, R.F. Tumor inhibitors. LIX. Jatrophone, a novel macrocyclic diterpenoid tumor inhibitor from Jatropha gossypiifolia. J. Amer. Chem. Soc. 1970, 92, 4476-4477.

82. Perdue Jr, R.E. Kb cell culture. I. Role in discovery of antitumor agents from higher plants. J Nat Prod 1982, 45, 418-426.

83. Kimura, Y.; Baba, K.; Okuda, H. Inhibitory effects of active substances isolated from Cassia garrettiana heartwood on tumor growth and lung metastasis in lewis lung carcinoma-bearing mice (Part 1). Anticancer Res. 2000, 20, 2899-2906.

84. Kimura, Y.; Baba, K.; Okuda, H. Inhibitory effects of active substances isolated from Cassia garrettiana heartwood on tumor growth and lung metastasis in lewis lung carcinoma-bearing mice (Part 2). Anticancer Res. 2000, 20, 2923-2930.

85. Yang, C.; Lu, W.; Niu, J. Studies on the antitumor action of xiangshenboheyou (a mixture composed of Pelargonium graveolens and Sophora flavescens and other herbs). Chung Ts'ao Yao 1983, 14, 409-410.

86. Charlson, A.J. Antineoplastic constituents of some Southern African plants. J. Ethnopharmacol. 1980, 2, 323-335.

87. Furusawa, E; Chou, S.; Furusawa, S.; Hirazumi, A.; Dang, Y. Antitumor activity of Ganoderma lucidum, an edible mushroom, on intraperitoneally implanted lewis lung carcinoma in synergenic mice. Phytother. Res. 1992, 6, 300-304.

88. Lee, S.; Wei, Y.; Chen, C.; Wang, S.; Chen, K. Antitumor effects of Ganoderma lucidum. J. Chin. Med. 1995, 6, 1-12.

89. Min, B.; Lee, H.; Bae, K.; Gao, J.; Nakamura, N.; Hattori, M. Antitumor activity of cultured mycelia of Ganoderma lucidum. Nat. Prod. Sci. 2002, 8, 52-55.

90. Kimura, Y.; Taniguchi, M.; Baba, K. Antitumor and antimetastatic effects on liver of triterpenoid fractions of Ganoderma lucidum: Mechanism of action and isolation of an active substance. Anticancer Res. 2002, 22, 3309-3318.

91. Han, S.; Lee, C.; Jeon, Y.; Hong, N.; Yoo, I.; Yang, K.; Kim, H. The inhibitory effect of polysaccharides isolated from Phellinus linteus on tumor growth and metastasis. Immunopharmacol. 1999, 41, 157-164.

Molecules 2013, 18

7

92. Kyo, E.; Uda, N.; Suzuki, A.; Kakimoto, M.; Ushijima, M.; Kasuga, S.; Itakura, Y. Immunomodulation and antitumor activities of aged garlic extract. Phytomedicine 1998, 5, 259-267.

93. Kyo, E.; Uda, N.; Kasuga, S.; Itakura, Y.; Sumiyoshi, H. Garlic as an immunostimulant, immunomodulatory agents from plants (H Wagner,Ed.), Birkhauser Verlag, Basel, 1999, 273-288.

94. Burger, A.; Mengs, U.; Schuler, J.; Fiebig, H. Anticancer activity of an aqueous mistletoe extract (AME) in syngeneic murine tumor models. Anticancer Res. 2001, 21, 1965-1968.

95. Bradley, G.; Clover, A. Apparent response of small cell lung cancer to an extract of mistletoe and homoeopathic treatment. Thorax 1989, 44, 1047-1048.

96. Khwaja, T.; Dias, C.; Pentecost, S. Recent studies on the anticancer activities of mistletoe (Viscum album) and its alkaloids. Oncology 1986, 43 (Suppl), 42-50.

97. Cheng, Y.; Lee, S.; Harn, H.; Huang, H.; Chang, W. The extract of Hibiscus syriacus inducing apoptosis by activating p53 and aif in human lung cancer cells. Amer. J. Chinese Med. 2008, 36, 171-184.

98. Ulubelen, A.; Cole, Jr. Proteinaceous antitumor substances from plants Mirabilis multiflora. J. Pharm. Sci. 1966, 55, 1368-1370.

99. Perdue Jr, R.; Smith, R.; Wall, M.; Hartwell, J.; Abbott, B. Camptotheca acuminata (Nyssaceae). Source of camptothecin, an antileukemic alkaloid. Tech. Bull. 1415, Ars, Usda Washington, USA 1970.

100. Persinos, G.; Quimby, M.; Mott, A.; Farnsworth, N.; Abraham, D.; Fong, H.; Blomster, R. Studies on Nigerian plants. III. Biological and phytochemical screening of Lophira lanceolata and the isolation of benzamide. Planta Med. 1967, 15, 361-365.

101. Barchi, J.; Moore, R.; Patterson, G. Acutiphycin and 20,21-didehydroacutiphycin, new antineoplastic agents from the cyanophyte Oscillatoria acutissima. J. Amer. Chem. Soc. 1984, 106, 8193-8197.

102. Staniszewski, A.; Slesak, B.; Kolodziej, J.; Harlozinska-Szmyrka, A.; Nowicky, J. Lymphocyte subsets in patients with lung cancer treated with thiophosphoric acid alkaloid derivatives from Chelidonium majus L. (Ukrain). Drugs Exp. Clin. Res. 1992, 18, 63-67.

103. Anonymous. Polysaccharide neoplasm inhibitors from mollusks. Patent-Japan Kokai Tokkyo Koho-82 18,620, 1982, 8pp. Patent Microbiochemical Res Found, Tokyo, Japan.

104. Kumara, S.; Huat, B. Extraction, isolation and characterization of antitumor principle, alpha-hederin, from the seeds of nigella sativa. Planta Med. 2001, 67, 29-32.

105. Hirazumi, A.; Furusawa, E.; Chou, S.; Hokama, Y. Immunomodulation contributes to the anticancer activity of Morinda citrifolia (noni) fruit juice. Proc. West Pharmacol. Soc. 1996, 39, 7-9.

106. Loder, J.; Russell, G.; Tumor inhibitory plants. The alkaloids of Bruguiera sexangula and Bruguiera exaristata (Rhizophoraceae). Aust. J. Chem. 1969, 22, 1271.

107. Liu, J.; Huang, M.; Tao, Y. Anwuweizonic acid and manwuweizic acid, the putative anticancer active principle of Schisandra propinqua. Can. J. Chem. 1988, 66, 414-415.

108. Wang, Z.; Chen, Y.; Jin, G.; Lin, S. Combined therapy of brain metastasis in lung cancer. Chin. J. Integ. Trad. West Med. 1995, 1, 36-38.

Molecules 2013, 18

8

109. Wu, S. Preoperative intravenous drip of an anti-tumor Chinese herb preparation Brucea javanica oil emulsion (Ya Dan Zi Emulsion) for lung cancer. Shang-Hai I Hsueh 1991, 14, 273-275.

110. Hu, B.; Yang, N.; Liu, W.; Sha, H.; Yu, D. Estimation of integrations of various functional groups of Brucea javanica (L.) Merr. Oil. Bopuxue Zazhi 1991, 8, 433-440.

111. Su, S.; Et Al.; Chin, J. Treatment of lung cancer with brain metastasis by using intravenous drip of 10% emulsion of Brucea javanica seminal oil. Integ. Trad. West Med. 1985, 5, 86-88.

112. Mishra, L.; Singh, B.; Dagenais, S. Scientific basis for the treatment use of Withania somnifera (Ashwagandha). Altern. Med. Rev. 2000, 5, 334-346.

113. Singh, S.; Singh, D.; Gupta, M.; Singh, N.; Kohli, R. An experimental evaluation of antitumor activity of Withania somnifera (Ashwagandha) and Geriforte. Indian J. Pharmacol. 1979, 11, 65b.

114. Sorbera, L.; Castaner, R.; Leeson, P. Ae-941 oncolytic antipsoriatic treatment of age-related macular degeneration angiogenesis inhibitor. Drugs Future 2000, 25, 551-557.

115. Jiang, Y.; Chen, J.; Wu, Z; Lin, L.; Feng, S. Inhibitory effect of tea polyphenol on mice lung cancer induced by diethylstilbestrol combined with urethane. Weisheng Dulixue Zazhi 1998, 12, 7-9.

116. Brown, M. Green tea (Camellia sinensis) extract and its possible role in the prevention of cancer. Altern. Med. Rev. 1999, 4, 360-370.

117. Yang, G.; Wang, Z.; Kim, S.; Liao, J.; Seril, D.; Chen, X.; Smith, T.; Yang, C. Characterization of early pulmonary hyperproliferation and tumor progression and their inhibition by black tea in a 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone-induced lung tumorigenesis model with a/j mice. Cancer Res. 1997, 57, 1889-1894.

118. Saitoh, H.; Feng, W.; Matsuzawa, T.; Ikekawa, T.; Antitumor activity of Hypsizigus marmoreus. II. Preventive effect against lung metastasis of lewis lung carcinoma. Yakugaku Zasshi 1997, 117, 1006-1010.

119. Nanba, H.; Mori, K.; Toyomasu, T.; Kuroda, H. Antitumor action of shiitake (Lentinus edodes) fruit bodies orally administered to mice. Chem. Pharm. Bull. 1987, 35, 2453-2458.

© 2013 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/3.0/).