Melittin prevents liver cancer cell metastasis through inhibition of the Rac1-dependent pathway

• DOI: 10.1002/hep.22240
• Publication Date: 2008-02-07T15:16:40Z
• Authors: Shujing Liu; Mei Yu; Ying He; Lin Xiao; Fang Wang; Changcheng Song; Shuhan Sun; Changquan Ling; Zhiheng Xu
• Keywords: rac1 GTP-Binding Protein; 0301 basic medicine; Carcinoma, Hepatocellular; Cell Survival; MAP Kinase Kinase 4; Liver Neoplasms; Mice, Nude; Melitten; Xenograft Model Antitumor Assays; 3. Good health; Gene Expression Regulation, Neoplastic; Actin Cytoskeleton; Disease Models, Animal; Mice; 03 medical and health sciences; Cell Movement; Cell Line, Tumor; Animals; Humans; Neoplasm Metastasis; Signal Transduction

Melittin, a water-soluble toxic peptide derived from bee venom of

Apis mellifera

was reported to have inhibitory effects on hepatocellular carcinoma (HCC). However, its role in antimetastasis and the underlying mechanism remains elusive. By utilizing both HCC cell lines and an animal model based assay system, we found that Rac1, which has been shown to be involved in cancer cell metastasis, is highly expressed in aggressive HCC cell lines and its activity correlated with cell motility and cytoskeleton polymerization. In addition, Rac1-dependent activity and metastatic potential of aggressive HCC cells are remarkably high in both cellular and nude mouse models. We provide evidence here that melittin inhibits the viability and motility of HCC cells

in vitro

, which correlates with its suppression of Rac1-dependent activity, cell motility, and microfilament depolymerization. Furthermore, melittin suppresses both HCC metastasis and Rac1-dependent activity in nude mouse models. The specificity of the effect of melittin on Rac1 was confirmed in HCC cells both

in vitro

and

in vivo.

Conclusion:

Melittin inhibits tumor cell metastasis by reducing cell motility and migration via the suppression of Rac1-dependent pathway, suggesting that melittin is a potential therapeutic agent for HCC.