Anti-cancer chemoagents-triggered centrosome aberrance and its relationship with mitotic cell death in pancreatic cancer cells.

点击翻译按钮获取中文摘要

Anti-cancer chemotherapy constitutes the major approach of anti-cancer strategy. Such agents act by different mechanisms, but commit a similar cell death process on targeted cells. Centrosome overduplication could be documented as one event involving in radiation-induced cell death. In order to elucidate whether this centrosome abverrance is an unique outcome followed by nuclear DNA damage or a universal phenomenon in relation to cell apoptosis, in this study, we utilized a series of chemo-agents with different mechanism leading treated cells to apoptosis.Human pancreatic cancer cell lines Suit-2 and Capan-2 were used in these experiments. Anti-cancer chemo-agents used in the study included etoposide (VP-16), mitomycin (MMC), cisplatin and 5-fluorouracil (5-FU). Centrosomes were visualized with indirect immunofluorescent microscopy after labeled by special anti-α-tubulin and anti-pericentrin. Cell apoptosis was evaluated by the micronucleus formation and cell death was determined by measuring fluorescence intensity of propidium iodide.All used chemo-agents could cause some degree of centrosome abnormality in the two cell lines, even though distinct profile of the abnormality were present in different cells. VP-16-induced centrosome aberrance was apparently dose dependent. The continuous low dose VP-16 administration (1 μM) caused a marked multi-centrosome abnormality but only moderate cell death in Suit-2 cells. Same continuous treatment with 10 μM of VP-16 in turn resulted in high occurrence of micronuclei formation as well as that of multi-nuclear giant cell formation. We also observed more centrosome number abnormality within these giant cells.The frequent visualizations of multinuclear giant cells and centrosome aberrance provide a strong impression of mitosis failure, which in turn could contribute to mitosis cell death. However, the novel concept of mitosis failure would undergo more intensive investigation.