Post on 31-Mar-2023
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© Georg Thieme Verlag KG · DOI 10.1055/s-0030-1250407 · Planta Med · Pouny I et al.
PLAMED-2010-06-0597-OP.R2
Supporting Information
Protoflavonoids from Ferns Impair Centrosomal Integrity of Tumor Cells
Isabelle Pouny1, Chantal Etiévant2, Laurence Marcourt1, Isabelle Huc-Dumas1, Muriel
Batut1, Frédéric Girard2, Michel Wright2, and Georges Massiot1
Affiliation 1 Unité Mixte de Service 2597, Centre National de la Recherche Scientifique (CNRS) - Pierre
Fabre, 2 Unité Mixte de Recherche 2587, Centre National de la Recherche Scientifique (CNRS) - Pierre
Fabre,
Institut des Sciences et Technologies du Médicament de Toulouse (ISTMT), Toulouse, France
Correspondence
Dr. G. Massiot
Unité Mixte de Service 2597
Centre National de la Recherche Scientifique (CNRS) - Pierre Fabre, ISTMT
3 rue des Satellites
BP94244
31432 Toulouse Cedex 4
France
Tel. : +33/5/34321402
Fax: +33/5/34321414
georges.massiot@cnrs-dir.fr
Dr. M. Wright
Unité Mixte de Recherche 2587
Centre National de la Recherche Scientifique (CNRS) - Pierre Fabre
ISTMT, 3 rue des Satellites
BP94244
2
© Georg Thieme Verlag KG · DOI 10.1055/s-0030-1250407 · Planta Med · Pouny I et al.
31432 Toulouse Cedex 4
France
Tel. : +33/5/34321364
Fax: +33/5/34321350
michel.wright@istmt.cnrs.fr
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© Georg Thieme Verlag KG · DOI 10.1055/s-0030-1250407 · Planta Med · Pouny I et al.
Fig 1S 1H and 13C NMR spectra of compound 1 (CD3OD + CDCl3, 500MHz).
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© Georg Thieme Verlag KG · DOI 10.1055/s-0030-1250407 · Planta Med · Pouny I et al.
Fig 2S 1H and 13C NMR spectrum of compound 2 (CD3OD, 500MHz).
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© Georg Thieme Verlag KG · DOI 10.1055/s-0030-1250407 · Planta Med · Pouny I et al.
Table 1S List of ferns tested Plant name Family Plant part Mitose effect Psilotatae Psilotum triquetrum Psilotaceae Whole plant Lycopodiatae Huperzia gnidioides Lycopodiaceae Whole plant + Lycopodiella cernua Lycopodiaceae Whole plant Lycopodium annotinum Lycopodiaceae Aerial parts Lycopodium casuarinoides Lycopodiaceae Whole plant + Lycopodium cernuum Lycopodiaceae Aerial parts Lycopodium clavatum Lycopodiaceae Whole plant Lycopodium complanatum Lycopodiaceae Whole plant Lycopodium serratum Lycopodiaceae Whole plant Selaginella braunii Selaginellaceae Whole plant Selaginella doederleinii Selaginellaceae Whole plant Selaginella fissidentoides Selaginellaceae Whole plant Selaginella involvens Selaginellaceae Whole plant Selaginella kraussiana Selaginellaceae Whole plant Selaginella tamariscina Selaginellaceae Whole plant + Selaginella trichoclada Selaginellaceae Whole plant Selaginella uncinata Selaginellaceae Whole plant Equisetatae Equisetum arvense Equisetaceae Whole plant Equisetum arvense Equisetaceae Fresh aerial parts Equisetum debile Equisetaceae Aerial parts
Equisetum debile Equisetaceae Underground parts
Equisetum debile Equisetaceae Whole plant + Equisetum fluviatile Equisetaceae Stems + Equisetum hyemale Equisetaceae Whole plant Equisetum hyemale Equisetaceae Aerial parts
Equisetum hyemale Equisetaceae Underground parts
Equisetum palustre Equisetaceae Fresh aerial parts Equisetum pratense Equisetaceae Whole plant Equisetum ramosissimum Equisetaceae Whole plant + Equisetum ramosissimum Equisetaceae Fresh aerial parts Equisetum telmateia Equisetaceae Fresh aerial parts Filicatae Asplenium lineatum Aspleniaceae Leaves Asplenium nidus Aspleniaceae Leaves Asplenium prolongatum Aspleniaceae Whole plant Asplenium scolopendrium Aspleniaceae Aerial parts
Asplenium scolopendrium Aspleniaceae Underground parts
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© Georg Thieme Verlag KG · DOI 10.1055/s-0030-1250407 · Planta Med · Pouny I et al.
Asplenium trichomanes* Aspleniaceae Aerial parts Asplenium trichomanes* Aspleniaceae Aerial parts Blechnum attenuatum Blechnaceae Leaves Blechnum attenuatum Blechnaceae Stems Blechnum montbrisonis Blechnaceae Leaves Blechnum montbrisonis Blechnaceae Stems Blechnum occidentale Blechnaceae Whole plant
Blechnum orientale Blechnaceae Underground parts
Blechnum orientale* Blechnaceae Aerial parts Blechnum orientale* Blechnaceae Aerial parts Blechnum spicant Blechnaceae Aerial parts Blechnum spicant Blechnaceae Whole plant Struthiopteris eburnea Blechnaceae Underground
parts + Struthiopteris eburnea Blechnaceae Leaves Woodwardia japonica Blechnaceae Leaves Woodwardia japonica Blechnaceae Stems
Woodwardia japonica Blechnaceae Underground parts
Woodwardia unigemmata Blechnaceae Underground parts
Cyathea borbonica Cyatheaceae Leaves Cyathea excelsa Cyatheaceae Leaves Cyathea pubescens Cyatheaceae Fronds Cyathea spectabilis Cyatheaceae Aerial parts Cyathea spinulosa Cyatheaceae Leaves Cyathea spinulosa Cyatheaceae Stems Davallia tyermanii Davalliaceae Aerial parts
Davallia tyermanii Davalliaceae Underground parts +
Dennstaedtia davallioides Dennstaedtiaceae Whole plant Dennstaedtia scabra Dennstaedtiaceae Whole plant Histiopteris incisa Dennstaedtiaceae Whole plant Microlepia marginata* Dennstaedtiaceae Whole plant Microlepia marginata* Dennstaedtiaceae Whole plant
Microlepia strigosa Dennstaedtiaceae Underground parts
Microlepia strigosa Dennstaedtiaceae Aerial parts Odontosoria chusana* Dennstaedtiaceae Whole plant + Odontosoria chusana* Dennstaedtiaceae Whole plant + Onychium japonicum Dennstaedtiaceae Whole plant Pteridium aquilinum Dennstaedtiaceae Leaves Pteridium aquilinum Dennstaedtiaceae Stems
Pteridium aquilinum Dennstaedtiaceae Underground parts
Pteridium revolutum Dennstaedtiaceae Leaves Pteridium revolutum Dennstaedtiaceae Underground
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© Georg Thieme Verlag KG · DOI 10.1055/s-0030-1250407 · Planta Med · Pouny I et al.
parts
Pteridium revolutum Dennstaedtiaceae Stems Cibotium barometz* Dicksoniaceae Leaves Cibotium barometz* Dicksoniaceae Leaves
Cibotium barometz Dicksoniaceae Underground parts
Cibotium barometz* Dicksoniaceae Stems Cibotium barometz* Dicksoniaceae Stems + Phymatodes scolopendria Dipteridaceae Whole plant Allantodia metteniana Dryopteridaceae Leaves Allantodia metteniana Dryopteridaceae Underground
parts Arachniodes chinensis Dryopteridaceae Whole plant Arachniodes sporadosora Dryopteridaceae Whole plant Athyrium filix-femina Dryopteridaceae Aerial parts Athyrium niponicum var pictum Dryopteridaceae Aerial parts
Athyrium niponicum var pictum Dryopteridaceae Underground parts
Deparia lobato-crenata Dryopteridaceae Underground parts
Deparia lobato-crenata Dryopteridaceae Aerial parts Diplazium esculentum Dryopteridaceae Stems Diplazium esculentum Dryopteridaceae Leaves Diplazium donianum Dryopteridaceae Whole plant
Diplazium subsinuatum Dryopteridaceae Underground parts
Diplazium subsinuatum Dryopteridaceae Aerial parts Dryopteris affinis Dryopteridaceae Fronds
Dryopteris affinis Dryopteridaceae Underground parts
Dryopteris carthusiana Dryopteridaceae Whole plant +
Dryopteris crassirhizoma Dryopteridaceae Underground parts
Dryopteris erythrosora Dryopteridaceae Aerial parts +
Dryopteris erythrosora Dryopteridaceae Underground parts
Dryopteris filix-mas* Dryopteridaceae Underground parts
Dryopteris filix-mas Dryopteridaceae Aerial parts
Dryopteris filix-mas* Dryopteridaceae Underground parts
Dryopteris laeta Dryopteridaceae Underground parts
Dryopteris laeta Dryopteridaceae Leaves Dryopteris sieboldii Dryopteridaceae Whole plant +
Dryopteris varia Dryopteridaceae Underground parts +
Dryopteris varia Dryopteridaceae Aerial parts + Dryopteris wallichiana Dryopteridaceae Underground +
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© Georg Thieme Verlag KG · DOI 10.1055/s-0030-1250407 · Planta Med · Pouny I et al.
parts
Matteuccia intermedia Dryopteridaceae Underground parts +
Matteuccia intermedia Dryopteridaceae Stems + Matteuccia intermedia Dryopteridaceae Leaves + Matteuccia orientalis Dryopteridaceae Whole plant + Matteuccia struthiopteris Dryopteridaceae Aerial parts
Matteuccia struthiopteris Dryopteridaceae Underground parts
Onoclea sensibilis* Dryopteridaceae Aerial parts
Onoclea sensibilis* Dryopteridaceae Underground parts
Onoclea sensibilis* Dryopteridaceae Aerial parts
Onoclea sensibilis* Dryopteridaceae Underground parts
Polystichum aculeatum Dryopteridaceae Aerial parts
Polystichum aculeatum Dryopteridaceae Underground parts
Polystichum caryotideum Dryopteridaceae Underground parts
Polystichum falcatum Dryopteridaceae Aerial parts
Polystichum falcatum Dryopteridaceae Underground parts
Polystichum fortunei Dryopteridaceae Aerial parts
Polystichum fortunei Dryopteridaceae Underground parts
Polystichum fortunei Dryopteridaceae Whole plant Polystichum hecatopterum Dryopteridaceae Aerial parts
Polystichum hecatopterum Dryopteridaceae Underground parts
Polystichum lepidocaulon Dryopteridaceae Whole plant Polystichum macrophyllum Dryopteridaceae Underground
parts Polystichum macrophyllum Dryopteridaceae Leaves Polystichum munitum Dryopteridaceae Whole plant + Polystichum polyblepharum Dryopteridaceae Aerial parts
Polystichum polyblepharum Dryopteridaceae Underground parts
Polystichum rigens Dryopteridaceae Whole plant Polystichum setiferum Dryopteridaceae Aerial parts
Polystichum setiferum Dryopteridaceae Underground parts
Polystichum setiferum Dryopteridaceae Whole plant Polystichum tsus-simense Dryopteridaceae Aerial parts
Polystichum tsus-simense Dryopteridaceae Underground parts
Rumohra adiantiformis Dryopteridaceae Whole plant Tectaria decurrens Dryopteridaceae Whole plant Dicranopteris chinensis Gleicheniaceae Whole plant
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© Georg Thieme Verlag KG · DOI 10.1055/s-0030-1250407 · Planta Med · Pouny I et al.
Dicranopteris dichotoma Gleicheniaceae Underground parts
Dicranopteris linearis Gleicheniaceae Aerial parts Dicranopteris pectinata Gleicheniaceae Aerial parts Diplopterygium laevissimum Gleicheniaceae Leaves
Diplopterygium laevissimum Gleicheniaceae Underground parts
Diplopterygium laevissimum Gleicheniaceae Stems Sticherus flagellaris Gleicheniaceae Aerial parts Trichomanes hildebrandtii Hymenophyllaceae Whole plant Angiopteris fokiensis Marattiaceae Leaves Angiopteris fokiensis Marattiaceae Stems
Angiopteris fokiensis Marattiaceae Underground parts
Marattia fraxinea Marattiaceae Fronds Marattia fraxinea Marattiaceae Stems Marsilea quadrifolia Marsileaceae Whole plant Marsilea schelpiana Marsileaceae Whole plant Nephrolepis abrupta Nephrolepidaceae Aerial parts
Nephrolepis abrupta Nephrolepidaceae Underground parts
Nephrolepis auriculata Nephrolepidaceae Underground parts
Nephrolepis auriculata Nephrolepidaceae Aerial parts Nephrolepis biserrata Nephrolepidaceae Leaves Nephrolepis biserrata Nephrolepidaceae Stems Nephrolepis biserrata Nephrolepidaceae Fronds Oleandra distenta* Oleandraceae Leaves
Oleandra distenta Oleandraceae Underground parts
Oleandra distenta* Oleandraceae Leaves Oleandra distenta Oleandraceae Stems Ophioglossum thermale Ophioglossaceae Whole plant Osmunda japonica Osmundaceae Leaves
Osmunda japonica Osmundaceae Underground parts +
Osmunda japonica Osmundaceae Stems
Osmunda regalis Osmundaceae Underground parts
Osmunda regalis Osmundaceae Aerial parts
Osmunda vachellii Osmundaceae Underground
parts Osmunda vachellii Osmundaceae Stems Osmunda vachellii Osmundaceae Leaves Plagiogyria adnata Plagiogyriaceae Whole plant Plagiogyria euphlebia Plagiogyriaceae Stems Plagiogyria euphlebia Plagiogyriaceae Leaves Plagiogyria euphlebia Plagiogyriaceae Underground
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© Georg Thieme Verlag KG · DOI 10.1055/s-0030-1250407 · Planta Med · Pouny I et al.
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Plagiogyria japonica Plagiogyriaceae Leaves Plagiogyria stenoptera Plagiogyriaceae Underground
parts Plagiogyria stenoptera Plagiogyriaceae Leaves Aglaomorpha coronans Polypodiaceae Whole plant Colysis digitata Polypodiaceae Underground
parts + Colysis digitata Polypodiaceae Aerial parts
Drynaria bonii Polypodiaceae Underground parts
Drynaria fortunei Polypodiaceae Underground parts
Lemmaphyllum microphyllum Polypodiaceae Whole plant Lepisorus asterolepis Polypodiaceae Whole plant Lepisorus contortus Polypodiaceae Whole plant Lepisorus eilophyllus Polypodiaceae Whole plant Lepisorus macrosphaerus Polypodiaceae Aerial parts Lepisorus oligolepidus Polypodiaceae Whole plant Lepisorus tosaensis Polypodiaceae Whole plant Microsorum dilatatum Polypodiaceae Aerial parts +
Microsorum fortuni Polypodiaceae Underground parts
Microsorum fortuni Polypodiaceae Aerial parts Microsorum fortuni Polypodiaceae Whole plant Microsorum membranaceum Polypodiaceae Whole plant
Microsorum pteropus Polypodiaceae Underground parts
Microsorum pteropus Polypodiaceae Aerial parts Microsorum punctatum Polypodiaceae Fronds Neocheiropteris ovatus* Polypodiaceae Whole plant Neocheiropteris ovatus* Polypodiaceae Whole plant Neocheiropteris phyllomanes Polypodiaceae Whole plant Niphidium crassifolium Polypodiaceae Whole plant Platycerium alcicorne Polypodiaceae Leaves Platycerium alcicorne Polypodiaceae Shield leaves Platycerium alcicorne Polypodiaceae Fronds Platycerium alcicorne Polypodiaceae Shield leaves Pleopeltis phymatodes Polypodiaceae Leaves Pleopeltis phymatodes Polypodiaceae Stems
Pleopeltis phymatodes Polypodiaceae Underground parts
Polypodium cambricum Polypodiaceae Whole plant Polypodium decumanum Polypodiaceae Aerial parts
Polypodium decumanum Polypodiaceae Underground parts
Pyrrosia adnascens Polypodiaceae Underground parts
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© Georg Thieme Verlag KG · DOI 10.1055/s-0030-1250407 · Planta Med · Pouny I et al.
Pyrrosia adnascens Polypodiaceae Aerial parts Pyrrosia gralla Polypodiaceae Aerial parts + Pyrrosia lanceolata Polypodiaceae Leaves Pyrrosia lingua* Polypodiaceae Whole plant Pyrrosia lingua Polypodiaceae Aerial parts
Pyrrosia lingua Polypodiaceae Underground parts +
Pyrrosia lingua* Polypodiaceae Whole plant Pyrrosia mollis Polypodiaceae Aerial parts Pyrrosia pekinensis Polypodiaceae Aerial parts Pyrrosia petiolosa Polypodiaceae Whole plant Pyrrosia sheareri Polypodiaceae Leaves Acrostichum aureum Pteridaceae Fronds Acrostichum aureum Pteridaceae Stems Adiantum capillus-veneris* Pteridaceae Whole plant Adiantum capillus-veneris* Pteridaceae Whole plant Adiantum caudatum Pteridaceae Whole plant
Adiantum flabellulatum Pteridaceae Underground parts
Adiantum flabellulatum Pteridaceae Aerial parts Adiantum flabellulatum Pteridaceae Whole plant Adiantum raddianum Pteridaceae Aerial parts
Adiantum raddianum Pteridaceae Underground parts
Adiantum venustum Pteridaceae Whole plant Aleuritopteris argentea Pteridaceae Whole plant Cheilanthes duclouxii Pteridaceae Whole plant +
Coniogramme japonica* Pteridaceae Underground parts
Coniogramme japonica* Pteridaceae Underground parts
Coniogramme japonica Pteridaceae Aerial parts Pellaea falcata Pteridaceae Whole plant Pellaea rotundifolia Pteridaceae Whole plant
Pellaea ternifolia Pteridaceae Underground
parts Pellaea ternifolia Pteridaceae Aerial parts Pityrogramma calomelanos Pteridaceae Fronds + Pteris aquilina Pteridaceae Fronds Pteris cretica Pteridaceae Aerial parts Pteris ensiformis Pteridaceae Whole plant
Pteris fauriei Pteridaceae Underground parts
Pteris fauriei Pteridaceae Aerial parts Pteris maclurioides Pteridaceae Whole plant Pteris multifida Pteridaceae Stems
Pteris multifida Pteridaceae Underground parts
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© Georg Thieme Verlag KG · DOI 10.1055/s-0030-1250407 · Planta Med · Pouny I et al.
Pteris multifida Pteridaceae Leaves Pteris multifida Pteridaceae Whole plant Pteris multifida Pteridaceae Aerial parts
Pteris multifida Pteridaceae Underground parts
Pteris semipinnata* Pteridaceae Whole plant + Pteris semipinnata* Pteridaceae Whole plant Pteris tremula Pteridaceae Whole plant Anemia phyllitidis Schizaeaceae Whole plant Lygodium flexuosum Schizaeaceae Spores Lygodium japonicum Schizaeaceae Aerial parts Lygodium japonicum Schizaeaceae Whole plant Lygodium kerstenii Schizaeaceae Fronds Lygodium lanceolatum Schizaeaceae Fronds Lygodium scandens Schizaeaceae Aerial parts
Lygodium scandens Schizaeaceae Underground parts
Cyclosorus acuminatus Thelypteridaceae Whole plant
Cyclosorus dentatus Thelypteridaceae Underground parts
Cyclosorus dentatus Thelypteridaceae Aerial parts
Cyclosorus falcilobus Thelypteridaceae Underground parts +
Cyclosorus falcilobus Thelypteridaceae Stems + Cyclosorus falcilobus Thelypteridaceae Fronds + Cyclosorus interruptus Thelypteridaceae Fronds
Cyclosorus interruptus Thelypteridaceae Underground parts
Cyclosorus parasiticus Thelypteridaceae Whole plant + Cyclosorus penangianus Thelypteridaceae Whole plant
Cyclosorus tylodes Thelypteridaceae Underground parts
Cyclosorus tylodes Thelypteridaceae Aerial parts
Phegopteris decursive-pinnata Thelypteridaceae Underground parts +
Phegopteris decursive-pinnata Thelypteridaceae Leaves Thelypteris beddomei Thelypteridaceae Leaves Thelypteris beddomei Thelypteridaceae Stems + rhizome Thelypteris glanduligera* Thelypteridaceae Whole plant + Thelypteris glanduligera* Thelypteridaceae Whole plant Vittaria isoetifolia Vittariaceae Whole plant + *Samples in duplicate refer to different collections.
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© Georg Thieme Verlag KG · DOI 10.1055/s-0030-1250407 · Planta Med · Pouny I et al.
Table 2S Major phenotypic changes induced by 13 reference compounds including anticancer
drugs or mitotic blockers
The compounds were chosen for their various mechanisms of action to validate the phenotypic
assay. They were evaluated at two concentrations corresponding to 2 x and 4 x IC50. First
observations of the global population were performed including the evaluation of cell density,
proportion of mitotic cells and cell death. Then effects on interphasic and mitotic cells labelled for
-tubulin, -tubulin and DNA were evaluated.
In the column “phases”, the underlined term corresponds to the predominant phase in the mitotic
population.
Topo=topoisomerase, PM=prometaphase, M=metaphase, Lc= lagging chromosomes
(1) Hastie SB. Interactions of colchicine with tubulin. Pharmacol Ther 1991; 51: 377-401 (2) Kruczynski A, Barret JM, Etievant C, Colpaert F, Fahy J, Hill BT. Antimitotic and
tubulin-interacting properties of vinflunine, a novel fluorinated Vinca alkaloid. Biochem Pharmacol 1998; 55: 635-648
(3) Ootsu K, Kozai Y, Takeuchi M, Ikeyama S, Igarashi K, Tsukamoto K, Sugino Y, Tashira T, Tsukagoshi S, Sakurai Y. Effects of new antimitotic antibiotics, ansamitocins, on the growth of murine tumors in vivo and on the assembly of microtubules in vitro. Cancer Res 1980; 40: 1707-1717
(4) Samson F, Donoso JA, Heller-Bettinger I, Watson D, Himes RH. Nocodazole action on tubulin assembly, axonal ultrastructure and fast axoplasmic transport. J Pharmacol Exp Ther 1979; 208: 411-417
(5) Schiff PB, Fant J, Horwitz SB. Promotion of microtubule assembly in vitro by taxol. Nature 1979; 7: 665-667
(6) Mayer TU, Kapoor TM, Haggarty SJ, King RW, Schreiber SL, Mitchison TJ. Small molecule inhibitor of mitotic spindle bipolarity identified in a phenotype-based screen. Science 1999; 286: 971-974
(7) Ross W, Rowe T, Glisson B, Yalowich J, Liu L. Role of topoisomerase II in mediating epipodophyllotoxin-induced DNA cleavage. Cancer Res 1984; 44: 5857-5860
(8) Hsiang YH, Liu LF. Identification of mammalian DNA topoisomerase I as an intracellular target of the anticancer drug camptothecin. Cancer Res 1988; 48: 1722-1726
(9) Aubel-Sadron G, Londos-Gagliardi D. Daunorubicin and doxorubicin, anthracycline antibiotics, a physicochemical and biological review. Biochimie 1984; 66: 333-352
(10) Hoshikawa Y, Kwon HJ, Yoshida M, Horinouchi S, Beppu T. Trichostatin A induces morphological changes and gelsolin expression by inhibiting histone deacetylase in human carcinoma cell lines. Exp Cell Res 1994; 214: 189-197
(11) Kovacs M, Toth J, Hetenyi C, Malnasi-Csizmadia A, Sellers JR. Mechanism of blebbistatin inhibition of myosin II. J Biol Chem 2004; 279: 35557-35563
(12) Harrington EA, Bebbington D, Moore J, Rasmussen RK, Ajose-Adeogun AO, Nakayama T, Graham JA, Demur C, Hercend T, Diu-Hercend A, Su M, Golec JM, Miller KM. VX-680, a potent and selective small-molecule inhibitor of the Aurora kinases, suppresses tumor growth in vivo. Nat Med 2004; 10: 262-267
(13) Adams J, Behnke M, Chen S, Cruickshank AA, Dick LR, Grenier L, Klunder JM, Ma YT, Plamondon L, Stein RL. Potent and selective inhibitors of the proteasome: dipeptidyl boronic acids. Bioorg Med Chem Lett 1998; 8: 333-338
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© Georg Thieme Verlag KG · DOI 10.1055/s-0030-1250407 · Planta Med · Pouny I et al.
Cell density Mitotic cells Cell death Cell morphology nuclei -tubulin centrosomes Phases chromosomes mitotic spindle centrosomes
x 2 low low blebbing irregular-shaped nuclei + disorganized microtubule network normal or surnumerary PM, M Lc in M 2 close poles of microtubules or
more than 2 polesnormal or
supernumerary
x 4 very low high blebbing irregular-shaped nuclei + disorganized microtubule network normal or surnumerary PM normal no microtubule normal
x 2 low low rounded cells ++ irregular-shaped nuclei ++; micronuclei ++
disorganized microtubule network normal or surnumerary PM, M Lc in M close poles or 3 poles supernumerary
x 4 very low low rounded cells + fragmented nuclei; micronuclei ++
disorganized microtubule network surnumerary PM normal multipolar. Low density of
microtubules. supernumerary
x 2 high = very low rounded cells + irregular-shaped nuclei + normal normal or surnumerary all Lc in M close poles supernumerary
x 4 medium low rounded cells ++; protrusions
irregular-shaped nuclei +; fragmented nuclei ++
microtubules in protrusions and cytoplasmic bridges normal or surnumerary PM, M Lc in M close poles or 3 poles supernumerary
x 2 medium low normal fragmented nuclei; micronuclei + disorganized microtubule network surnumerary PM normal multipolar supernumerary
x 4 medium low normal fragmented nuclei; micronuclei + disorganized microtubule network surnumerary PM normal multipolar supernumerary
x 2 medium low normal fragmented nuclei; micronuclei + normal surnumerary and scattered all, PM Lc in M multipolar normal or supernumerary
x 4 very low low rounded cells + fragmented nuclei; micronuclei + disorganized microtubule network surnumerary and scattered PM normal multipolar, spindles of dense
microtubules supernumerary
x 2 low very low rounded cells + irregular-shaped nuclei + disorganized microtubule network normal P, PM normal monopolar gathered
x 4 very low high rounded cells ++ irregular-shaped nuclei ++; fragmented nuclei +
disorganized microtubule network normal PM hypercondensed
chromosomes monopolar gathered
x 2 low none low normal binucleation normal 2 scattered centrosomes or surnumerary
x 4 very low none high rounded cells ++ low density nucleimicrotubule ring around nuclei,
disorganized microtubule network
3 scattered centrosomes or surnumerary
x 2 low none very low normal micronuclei + microtubule ring around nuclei normal
x 4 low none low rounded cells + binucleation; micronuclei + microtubule ring around nuclei normal
x 2 medium none very low rounded cells + binucleation normal normal
x 4 medium none very low rounded cells ++; protrusions; blebbing micronuclei + microtubule ring around nuclei normal
x 2 medium = very low protrusions + normal 1 to 3 protrusions with microtubules per cell normal all Lc in M mainly normal spindles. Some
tripolar PM normal
x 4 low low protrusions ++ irregular-shaped nuclei + 1 to 4 protrusions with microtubules per cell normal PM normal multipolar supernumerary
x 2 very high = low protrusions, cytoplasmic bridges binucleation microtubules in protrusions and
cytoplasmic bridgessurnumerary in binucleated
cells all normal wide midbody normal
x 4 very high = high protrusions, cytoplasmic bridges binucleation microtubules in protrusions and
cytoplasmic bridgessurnumerary in binucleated
cells all normal wide midbody normal
x 2 high = very low blebbing fragmented nuclei +; polylobed nuclei +
disorganized microtubule network surnumerary PM normal monopolar normal
x 4 high low blebbing fragmented nuclei +; polylobed nuclei +
disorganized microtubule network surnumerary PM normal monopolar; short microtubules normal
x 2 high very low rounded cells ++; protrusions normal disorganized microtubule
network surnumerary PM, M normal monopolar normal
x 4 high none low rounded cells ++; protrusions normal disorganized microtubule
network none or surnumerary none
Interphase
Camptothecin (1,4.10-6 M)
Doxorubicin (2,0.10-7 M)
Trichostatin A (8,0.10-8 M)
Ansamitocin P-3 (5,7.10-11 M)
Vinflunine (3,4.10-8 M)
Taxol (2,0.10-9 M)
Monastrol (5,1.10-5 M)
HDACs (10)
Kinesin Eg5 (6)
tubulin (2)
tubulin (3)
tubulin (5)
Blebbistatin (>1,0.10-5 M)
Myosin (11)
Topo. II (7)
Topo. I (8)
DNA (9)
Nocodazole (4,7.10-8 M)
tubulin (4)
Colchicine (7,0.10-9 M)
General qualitative observationsTreatment (IC50 on
HeLa cells)IC50
ratioTarget
tubulin (1)
PS341 (9,8.10-8 M)
Proteasome (13)
Etoposide (3,2.10-5 M)
VX680 (4,2.10-7 M)
Aurora B (12)
none
Mitosis
none
none