RT Journal Article SR Electronic T1 Antiproliferative Activity and Induction of Apoptosis in Human Melanoma Cells by Houttuynia cordata Thunb Extract JF Anticancer Research JO Anticancer Res FD International Institute of Anticancer Research SP 6619 OP 6628 VO 37 IS 12 A1 MONGKOL YANAROJANA A1 THAMTHIWAT NARARATWANCHAI A1 SARUT THAIRAT A1 SALUNYA TANCHAROEN YR 2017 UL http://ar.iiarjournals.org/content/37/12/6619.abstract AB Background/Aim: To analyze the apoptotic effect of Houttuynia cordata Thunb (HCT) extract on human melanoma A375 cells and its underlying mechanisms. Materials and Methods: The effects of HCT on cell death were determined using the MTT assay. Hoechst 33342 staining was conducted to confirm the detection of cell apoptosis. Caspase-3 and caspase-8 mRNA and cleaved protein levels were investigated by RT-PCR and western blotting, respectively. The release of high mobility group box 1 (HMGB1) and phosphorylation of mitogen-activated protein kinase (MAPK) were determined by ELISA. Results: Caspase-3 and caspase-8 specific inhibitors suppressed HCT-induced cell death. HCT increased caspase-3 and caspase-8 mRNA, protein levels, and caspase activities in a concentration- and time-dependent manner. HCT induced MAPK phosphorylation in a time-dependent fashion. Pretreatment of cells with a selective inhibitor of p38 MAPK reduced apoptosis and reversed the levels of HMGB1 release in response to HCT treatment. Conclusion: HCT induces A375 programmed cell death by activating the caspase-dependent pathway and by p38 phosphorylation associated with HMGB1 reduction.