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	Ai-Ping Le, Lun-Li Zhang, Wei Liu, Yu-Fei Shi
Journal	Oncology reports (Oncol Rep) Vol. 35 Issue 5 Pg. 2970-6 (May 2016) ISSN: 1791-2431 [Electronic] Greece
PMID	26986084 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	Antineoplastic Agents CCND1 protein, human CTNNB1 protein, human beta Catenin Cyclin D1 Lithium Chloride Cantharidin
Topics	Animals Antineoplastic Agents (pharmacology) Apoptosis Cantharidin (pharmacology) Carcinoma, Hepatocellular (drug therapy, pathology) Cell Proliferation Cell Self Renewal Cyclin D1 (metabolism) Drug Screening Assays, Antitumor G2 Phase Cell Cycle Checkpoints (drug effects) Hep G2 Cells Humans Lithium Chloride (pharmacology) Liver Neoplasms (drug therapy, pathology) Male Mice, Inbred BALB C Mice, Nude Neoplasm Transplantation Neoplastic Stem Cells (drug effects, physiology) beta Catenin (metabolism)

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