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.
Svechnikova
Irina
I
Department of Woman and Child Health, Pediatric Endocrinology Unit, Karolinska Institute & University Hospital, Q2:08, SE-171 76 Stockholm, Sweden. Irina.Svechnikova@ki.se
Ammerpohl
Ole
O
Ekström
Tomas J
TJ
D017209:Apoptosis / Q000235:genetics / Q000502:physiology*; D006528:Carcinoma, Hepatocellular / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000502:physiology; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D056572:Histone Deacetylase Inhibitors; D006801:Humans; D008113:Liver Neoplasms / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology
C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors