Evaluation of the Apoptotic and Antiproliferative Activities of Paclitaxel in Ehrlich Ascites Tumor Cells

ABSTRACT

Taxol (paclitaxel, PAC) is a diterpene with antitumor activity against a variety of human neoplasms. PAC cytotoxicity is thought to derive mainly from a stabilization of microtubules as a result of enhanced tubulin polymerization that leads to an accumulation of cells in G₂/M phase of cell cycle. In this study, the cytotoxic effect occurred by PAC in tumor cells in vitro were examined. Mouse mammary gland carcinoma-derived Ehrlich Ascites Tumor Cells (EATC) were employed as tumor cell line. Results of the experiments were evaluated with cell kinetic parameters such as growth rate, mitotic index, apoptotic index and DNA fragmentation. IC₃₀ and IC₅₀ concentrations of PAC (6 μg/ml and 12 μg/ml, respectively) were applied to the cell line for 0–24 hours. The proliferation rate of EATC was inhibited by PAC concentrations compared to control with increasing treatment time (2–24 hours). The inhibition of growth rate was higher in 12 μg/ml PAC treatment than those in 6 μg/ml treatment. In our studies, when the mitotic index parameter data was evaluated to determine which phase of the cell cycle was affected by PAC to cause the repression of cell reproduction, it was found that PAC exposes its cytotoxic effect by causing cell accumulation at mitosis. The accumulation of the cells resulted in an increase in mitotic index values, which was an expected consequence of PAC treatment. In addition to the effect of PAC on mitotic cell accumulation, the results on its effect on apoptotic index parameter support the findings about its repressive function on cell reproduction and its effect on mitotic index increase. It was observed that depending on the drug treatments, increase of mitotic index, inhibition of growth rate and apoptotic index in EATC were increased with respect to control, being of statistically significant (p<0.01-p<0.001). And the DNA fragmentation levels of EATC induced by PAC increased significantly.