Comparison of cell death-inducing effect of novel taxane SB-T-1216 and paclitaxel in breast cancer cells.
BACKGROUND
In this study, the effect of novel taxane SB-T-1216 and paclitaxel on sensitive MDA-MB-435 and resistant NCI/ADR-RES human breast cancer cells was compared.


METHODS
Cell growth and survival were evaluated after 96-hour incubation with tested concentrations of taxanes. The effect on the formation of microtubule bundles was assessed employing fluorescence microscopy and on the cell cycle employing flow cytometric analysis. The activity of caspases was assessed employing commercial colorimetric kits.


RESULTS
The IC(50) (concentration resulting in 50% of living cells in comparison with the control) of SB-T-1216 in sensitive cells was 0.6 nM versus 1 nM for paclitaxel. However, the IC(50) of SB-T-1216 in resistant cells was 1.8 nM versus 300 nM for paclitaxel. Both SB-T-1216 and paclitaxel at death-inducing concentrations induced the formation of microtubule bundles in sensitive as well as resistant cells. Cell death induced in sensitive and resistant cells by paclitaxel was associated with the accumulation of cells in the G(2)/M phase. On the contrary, cell death induced by SB-T-1216 took place without the accumulation of cells in the G(2)/M phase but with a decreased number of G(1) cells and the accumulation of hypodiploid cells. Both SB-T-1216 and paclitaxel activated caspase-3, caspase-9, caspase-2 and caspase-8 in sensitive as well as resistant cells.


CONCLUSIONS
Cell death induced by both paclitaxel and novel taxane SB-T-1216 in breast cancer cells is associated with caspase activation and with the formation of interphase microtubule bundles. Novel taxane SB-T-1216, but not paclitaxel, seems to be capable of inducing cell death without the accumulation of cells in the G(2)/M phase.
Kovár
Jan
J
Department of Cell and Molecular Biology, Third Faculty of Medicine, Charles University, Ruská 87, 10000 Prague 10, Czech Republic. jan.kovar@lf3.cuni.cz
Ehrlichová
Marie
M
Smejkalová
Barbora
B
Zanardi
Ilaria
I
Ojima
Iwao
I
Gut
Ivan
I
D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D053143:Caspase 2 / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D053181:Caspase 8 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D004317:Doxorubicin / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm; D016193:G1 Phase / Q000187:drug effects; D016195:G2 Phase / Q000187:drug effects; D006801:Humans; D008856:Microscopy, Fluorescence; D008870:Microtubules / Q000187:drug effects; D017239:Paclitaxel / Q000494:pharmacology*; D043823:Taxoids / Q000494:pharmacology*
D000903:Antibiotics, Antineoplastic; D000972:Antineoplastic Agents, Phytogenic; D043823:Taxoids; D004317:Doxorubicin; D053143:Caspase 2; D053148:Caspase 3; D053181:Caspase 8; D053453:Caspase 9; D017239:Paclitaxel