Study On Relations Of Apoptosis And Reactive Oxygen Species (ROS) Production In Cell Cultures Induced By Docetaxel

Establish a model of docetaxel-treated acute myelomoncytic leukemia (AML) HL60 and chronic myeogenous leukemia (CML) K562 in vitro. Study on the apoptotic systems induced by docetaxel in HL60 and K562 cells. Compare the effects of free radical on the two cell lines. Find the relations between ROS and apoptosis in HL60 and K562 cells. Establish a mathematical model of K562 cells growth and treatment with the antimitotic agent docetaxel in vitro. Results: â‘ Growth of two cell lines was inhibited obviously by docetaxel. â‘¡The kinetics of cytotoxicity following continuous exposure to docetaxel showed a 24 hours delayed response in K562 cells. â‘¢Docetaxel induced the production of intracellular ROS in HL60 cells and the peak level was presented at 24h; Extracellular superoxide anion was secreted obviously in HL60 cells after 24h treatment with docetaxel and peaked at 36h. â‘£The changes of SOD and CAT activity in HL60 were obvious. But it was not evident in K652 cells. ⑤Addition of DPI, CAT and NAC attenuated HL60 cell death and apoptosis, but DMSO did not effect on cellular apoptosis. These showed that K562 had an effective antioxidant system that inhibits the generation of ROS induced by docetaxel. And HL60 had a poor antioxidant system permitting docetaxel to induce the generation of ROS. Further analyze showed that docetaxel-induced ROS production was directly involved in apoptotic events. We next found that the proapoptotic ROS were mainly O₂^-and H₂O₂ . Analysis of the FCM data showed that docetaxel caused a decrease in the m-phase transition in K562 cells. A model of in vitro cancer cell growth and docetaxel interaction has been presented and adapted to the growth and treatment of K562 cell line. Cells always grow exponentially. The model shows that the maximum docetaxel concentration to cause m-phase transition is 17.9631nM, and the maximum docetaxel concentration to induce apoptosis is 7.8192nM. The model predicts that m-phase transition is not relation to apoptosis.