title: Cantharidin inhibits cell proliferation and induces apoptosis through G2/M phase cell cycle arrest in hepatocellular carcinoma stem cells.
abstract: The present study was designed to investigate the effect of cantharidin on cell proliferation, ability of selfrenewal, cell cycle arrest and induction of apoptosis in HepG2 hepatocellular carcinoma stem cells (HCSCs). It was observed that cantharidin treatment exhibited dose- and time-dependent inhibitory effect on the viability of HCSCs. The inhibition of cell viability by cantharidin in HepG2 CD133+ and parental cells was significant at the concentration 5 and 15 µM, respectively after 48 h. Cantharidin treatment inhibited the self-renewal ability of the HCSCs and the expression of β-catenin and cyclin D1. Flow cytometry revealed that cantharidin treatment at 5 µM concentration significantly increased the cell population in G2/M phase and decreased the population in the G1 phase. Cantharidin treatment in the HCSCs for 48 h increased expression of histone H2AX, Myt1, cyclin A2, cyclin B1, p53 and cdc2 (Tyr15) phosphorylation significantly compared to the parental cells. Exposure of the HCSCs to cantharidin for 48 h at a concentration of 5 µM caused a significant increase in the proportion of apoptotic cells. Therefore, cantharidin is a promising agent for the hepatocellular carcinoma treatment.
authors.affiliation: Department of Blood Transfusion, First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, P.R. China.
authors.forename: Ai-Ping
authors.initials: AP
authors.lastname: Le
authors.affiliation: Department of Infectious Diseases, First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, P.R. China.
authors.forename: Lun-Li
authors.initials: LL
authors.lastname: Zhang
authors.affiliation: Department of Blood Transfusion, First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.affiliation: Department of Infectious Diseases, First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, P.R. China.
authors.forename: Yu-Fei
authors.initials: YF
authors.lastname: Shi
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D002193:Cantharidin / Q000494:pharmacology*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy / Q000473:pathology; D049109:Cell Proliferation; D000066673:Cell Self Renewal; D019938:Cyclin D1 / Q000378:metabolism; D004354:Drug Screening Assays, Antitumor; D059565:G2 Phase Cell Cycle Checkpoints / Q000187:drug effects*; D056945:Hep G2 Cells; D006801:Humans; D018021:Lithium Chloride / Q000494:pharmacology; D008113:Liver Neoplasms / Q000188:drug therapy / Q000473:pathology; D008297:Male; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D014411:Neoplastic Stem Cells / Q000187:drug effects* / Q000502:physiology; D051176:beta Catenin / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; C530104:CCND1 protein, human; C495270:CTNNB1 protein, human; D051176:beta Catenin; D019938:Cyclin D1; D018021:Lithium Chloride; D002193:Cantharidin