Cisplatin-induced p53-independent growth arrest and cell death in cancer cells

In a recent study, it was shown that DNA damaging agent cisplatin-induced g rowth arrest and cell death in cancel cells by a pathway sharing some of th e characteristics of replicative senescence. The aim of this study was to d etermine the role of p53, p21(WAF1) and p16(INK4A) proteins in this alterna tive route to cancer cell death in additional human cancer cell lines. Afte r exposure to cisplatin, all the cell lines underwent growth arrest and exp ressed the senescence marker senescence-associated beta-galactosidase, but showed none of the features of apoptosis. However, there was no change in p 53 protein expression, and neither p21(WAF1) nor p16(INK4A) was expressed b efore or up to 4 days after cisplatin exposure. These findings provide furt her evidence that cells carrying mutations resulting in loss of function in the p53 gene can be killed by cisplatin via a p53-independent route with s ome similarities to replicative senescence, but not apoptosis.