Apoptotic cell death induced by baccatin III, a precursor of paclitaxel, may occur without G(2)/M arrest

Purpose: Paclitaxel has been demonstrated to possess significant cell-killi ng activity in a variety of tumor cells by induction of apoptosis, but the mechanism by which paclitaxel leads to cell death and its relationship with mitotic arrest is not entirely clear. In this study, baccatin III, a synth etic precursor of paclitaxel, was used to analyze whether paclitaxel-induce d apoptosis can be a separate event from microtubule bundling and G(2)/M ar rest. Methods: Several different methods including DNA fragmentation, flow cytometric analyses, TdT-mediated dUTP nick end labeling (TUNEL) and time-l apse video microscopy were used to analyze apoptotic cell death induced by baccatin III and its possible correlation with cell cycle distribution. Res ults: Our results demonstrated that baccatin III could also cause apoptotic cell death in both BCap37 (a human breast cancer cell line) and KB cells ( derived from human epidermoid carcinoma), but had less effect on microtubul e bundling and G(2)/M arrest. Furthermore, we demonstrated that most apopto tic events induced by baccatin III were not coupled with G(2)/M arrest. Ins tead, these apoptotic events occurred predominantly in the cells in other p hases of the cell cycle. Conclusion: Baccatin III, which contains the core taxane ring, is the fundamental piece of paclitaxel structure. The finding of baccatin III-induced apoptosis independent of cell cycle arrest, on the one hand, implies that the core taxane ring may play a critical role in ind ucing cell death and, on the other hand, suggests that paclitaxel might ind uce apoptosis from other phases of the cell cycle by a similar mechanism.