Methyl-Cantharidimide Inhibits Growth of Human Hepatocellular Carcinoma Cells by Inducing Cell Cycle Arrest and Promoting Apoptosis

Xiangzhong Huang; Wen Xie; Xiaofan Yu; Caiyun Fan; Jin Wang; Yi Cao; Jianxiang Li

doi:10.3389/fonc.2019.01234

Methyl-Cantharidimide Inhibits Growth of Human Hepatocellular Carcinoma Cells by Inducing Cell Cycle Arrest and Promoting Apoptosis

Front Oncol. 2019 Nov 15:9:1234. doi: 10.3389/fonc.2019.01234. eCollection 2019.

Authors

Xiangzhong Huang¹, Wen Xie², Xiaofan Yu², Caiyun Fan², Jin Wang², Yi Cao², Jianxiang Li²

Affiliations

¹ Department of Interventional Therapy, Affiliated Jiangyin Hospital, Medical College of Southeast University, Jiangyin, China.
² School of Public Health, Medical College of Soochow University, Suzhou, China.

Abstract

Methyl-Cantharidimide (MCA) is a derivative of cantharidin which has potential anticancer activity. This study investigates the effect of MCA on the growth and metastasis of human hepatocellular carcinoma (HCC) cells. Human HCC HepG2 and Hep3B2.1-7 cells, and normal hepatocytes (L02) were treated with a series of concentrations of MCA. The inhibition ability of these cells was examined by CCK-8 assay. Cell cycle and cell apoptosis were determined using Flow Cytometry. The effect of MCA on cell migration and invasion was evaluated through scratch wound healing and transwell migration assays. Furthermore, Western blot was used to evaluate biomarkers associated with cell cycle and apoptosis. It was found that: (i) MCA inhibited cell proliferation in HCC cells in a dose- and time-dependent manner, especially in HepG2 cells; (ii) MCA arrested HCC cells in G-1 phase cell cycle; (iii) MCA induced HCC cells apoptosis; (iv) MCA inhibited the migration ability of HCC cells; and (v) MCA treatment significantly increased cleaved-caspase3 and decreased NF-κB protein in HCC cells. These results suggest that MCA has cytotoxic effect on HCC cells by inducing cell cycle arrest and promoting apoptosis. MCA could be developed as an previous anticancer drug for the treatment of human hepatocellular carcinoma.

Keywords: cantharidin (CTD); cell growth; hepatocellular carcinoma; invasion; methyl-cantharidimide (MCA).