# The effect of paclitaxel on apoptosis, autophagy and mitotic catastrophe in AGS cells

## TL;DR

This study shows how paclitaxel causes cell death in AGS gastric cancer cells through mitotic catastrophe, autophagy, and apoptosis.

## Contribution

The paper identifies mitotic catastrophe as a key mechanism of paclitaxel-induced cell death in AGS cells, alongside apoptosis and autophagy.

## Key findings

- Paclitaxel activates intrinsic apoptosis via caspase-3, caspase-9, and PARP in AGS cells.
- Paclitaxel induces autophagy, as shown by increased LC3B-II, Atg5, and Beclin-1 levels.
- Paclitaxel causes mitotic catastrophe and G2/M phase arrest, leading to cell death within 48 hours.

## 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.