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.

Highlights

  • Hepatocellular carcinoma (HCC) is a primary malignant tumor in the liver

  • Since MCA inhibits hepatocellular carcinoma (HCC) cell proliferation, we examine whether MCA affects cell cycle progression in HCC cells by flow cytometry

  • Because MCA induces apoptosis of HCC cells, we explored whether the molecules that regulate cell apoptosis were involved

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Summary

Introduction

Hepatocellular carcinoma (HCC) is a primary malignant tumor in the liver. It is the third leading cause of cancer deaths worldwide. The annual incidence of HCC in North America and Western Europe ranges from 10 to 15 cases per 100,000 people, while in parts of Africa and Asia, the incidence is much higher and range from 50 to 150 cases per 100,000 people [1]. The median survival following diagnosis ranges from ∼6 to 20 months. Tumor resection is an option of choice for the treatment of HCC. Since most of the diagnosis is made in late stages of the disease, HCC patients have few opportunity to undergo surgery. There is an urgent need for early diagnosis and effective therapeutic medication [2, 3]. There were several reports suggest that some traditional Chinese medicines showed remarkable

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