Abstract
Paclitaxel is an anti-microtubule agent that has been shown to induce cell death in gastric cancer. However, the detailed mechanism of action is unclear. In this study, we reveal that the paclitaxel-induced cell death mechanism involves mitotic catastrophe, autophagy and apoptosis in AGS cells. Paclitaxel induced intrinsic apoptosis by activating caspase-3, caspase-9 and PARP. In addition, the significant increase in autophagy marker LC3B-II, together with Atg5, class III PI3K and Beclin-1, and the down-regulation of p62 following paclitaxel treatment verified that paclitaxel induced autophagy. Further experiments showed that paclitaxel caused mitotic catastrophe, cell cycle arrest of the accumulated multinucleated giant cells at the G2/M phase and induction of cell death in 24 h. Within 48 h, the arrested multinucleated cells escaped mitosis by decreasing cell division regulatory proteins and triggered cell death. Cells treated with paclitaxel for 48 h were grown in fresh medium for 24 h and checked for CDC2, CDC25C and lamin B1 protein expressions. These proteins had decreased significantly, indicating that the remaining cells became senescent. In conclusion, it is suggested that paclitaxel-induced mitotic catastrophe is an integral part of the cell death mechanism, in addition to apoptosis and autophagy, in AGS cells.
Highlights
Autophagy plays an important regulatory role in cell survival and cell death, depending on the cell environment and cell type
The present study suggests that paclitaxel induces cell death through apoptosis, autophagy and mitotic catastrophe in AGS cells
The involvement of autophagy was analysed in paclitaxel-treated AGS cells
Summary
Autophagy plays an important regulatory role in cell survival and cell death, depending on the cell environment and cell type. Paclitaxel induced LC3B activation, as evidenced by the enhanced intensity of green fluorescence when the cells were exposed to immunofluorescence staining using anti-LC3B antibody, and expression of the LC3B-II/LC3B-I ratio was increased in western blot analysis. Pretreatment with 5 mM 3-MA, the class III PI3K inhibitor[42], decreased paclitaxel-induced LC3B-II protein expression. From these results, it was suggested that paclitaxel induced autophagy in AGS cell
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
