Effects of low and high concentrations of antitumour drug taxol in anaplastic thyroid cancer cells.
OBJECTIVE
To study the changes of cell cycle, mitochondrial membrane potential and caspase activation in response to an antitumour drug Taxol in ARO and KTC-2 cell lines of anaplastic thyroid carcinoma.


METHODS
Experiments were done on thyroid anaplastic cancer cell lines ARO and KTC-2 using Western blotting, flow cytometry, light and fluorescent microscopy.


RESULTS
Taxol significantly activated caspases in ARO cells starting from drug concentration of 5 nM. Maximum activation was observed at 25 nM and further increase of Taxol concentration to 100 nM resulted in a reduction of caspase activation. Concomitant to caspase activation, a loss of mitochondrial membrane potential was observed. At Taxol concentration of 100 nM, most cells lost their mitochondrial membrane potential. Low Taxol concentrations (10 nM) caused changes in the cell cycle that are typical for apoptosis without cell cycle arrest. Higher drug doses starting from 50 nM arrested cell cycle in G2/M phase. In KTC-2 cell line Taxol concentration as low as 1 nM induced apoptosis. 6-15 nM of the drug caused massive (75-83%) cell death. Upon Taxol action, the increase in the number of cells displaying manifestations of accelerated senescence was insignificant.


CONCLUSIONS
Taxol induces bona fide apoptosis in thyroid cancer cell cultures at low (1-25 nM) concentrations. Higher drug doses cause the loss of mitochondrial membrane potential and possibly lead to other types of cell death. No accelerated senescence at different Taxol concentrations was observed. The significance of subG1 and G2/M cell populations at low and high doses of Taxol is discussed.
Pushkarev
V M
VM
V.P.Komisarenko Institute of Endocrinology & Metabolism of AMS of Ukraine, Kyiv 04114, Ukraine. endo@i.kiev.ua
Starenki
D V
DV
Saenko
V A
VA
Yamashita
S
S
Kovzun
O I
OI
Popadiuk
I D
ID
Pushkarev
V V
VV
Tronko
M D
MD
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002277:Carcinoma / Q000188:drug therapy*; D020169:Caspases / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D017239:Paclitaxel / Q000494:pharmacology*; D013964:Thyroid Neoplasms / Q000188:drug therapy*
D000970:Antineoplastic Agents; D020169:Caspases; D017239:Paclitaxel