p21waf1/Cip1 partially mediates apoptosis in hepatocellular carcinoma cells.

p21waf1/Cip1 (p21) is a tumor suppressor gene involved in apoptosis in many cancer cell types induced by different agents. In spite of concomitant induction of p21 by many anti-cancer drugs, including inhibitors of histone deacetylases (HDACi), its pro-apoptotic action has been debated during the last several years due to a lack of direct evidence regarding the exact role of p21 in apoptosis. With the help of anti-sense p21 expression, we show here that p21 is mediating the apoptotic effects of HDACi 4-phenylbutyrate (4-PB) and Trichostatin A (TSA) on the hepatocellular hepatocarcinoma Hep3B cells. Hep3B cells were transfected by EGFP-p21 anti-sense or sense plasmids, and apoptosis induced by HDACi was assessed by TUNEL assay. The results show that the p21 anti-sense construct prevents apoptosis, induced by HDAC inhibitors in Hep3B cells. The obtained results suggest an important role for p21 in mediating the apoptotic effect of HDACi.