P21WAF1/CIP1 is dispensable for G1 arrest, but indispensable for apoptosis induced by sodium butyrate in MCF-7 breast cancer cells

Abstract

Sodium butyrate (NaB) has been proposed as a potential anticancer agent. However, its mechanism of action is not totally elucidated. Here, we showed that NaB-induced cell cycle arrest and apoptosis were associated with an increase of P21waf1/cip1 in MCF-7 breast cancer cells. This increase was more important in the nuclei, as revealed by immunofluorescence analysis. Transient transfections of MCF-7 cells with p21 deficient for interaction with CDK, but not with p21 deficient for interaction with PCNA (p21PCNA-), abrogated NaB-induced cell cycle arrest. This indicated that cell cycle blockage involved the interaction of p21waf1/cip1 with CDK. However, P21 waf1/cip1 was dispensable, since p21 antisense did not modify cell cycle arrest. On the other hand, NaB-induced apoptosis was abolished by p21 antisense or p21PCNA-. In addition, NaB decreased PCNA levels, but increased the association of PCNA with P21waf1/cip1. These results suggested that NaB-induced apoptosis required P21waf1/cip1 and its interaction with PCNA.