MEL-pep, an analog of melittin, disrupts cell membranes and reverses 5-fluorouracil resistance in human hepatocellular carcinoma cells.

MEL-pep, an analog of melittin, disrupts cell membranes and reverses 5-fluorouracil resistance in human hepatocellular carcinoma cells. Int J Biochem Cell Biol. 2018 May 22;: Authors: Ke M, Dong J, Wang Y, Zhang J, Zhang M, Wu Z, Lv Y, Wu R Abstract Chemotherapy resistance represents a major obstacle in the treatment of patients with hepatocellular carcinoma (HCC). The purpose of this study was to investigate the anti-cancer effect of MEL-pep, a novel analog of the natural antibacterial peptide melittin (MEL), on human 5-fluorouracil-resistant HCC cells (BEL-7402/5-FU) and to clarify the molecular mechanisms involved in these effects. We found that MEL-pep inhibited the proliferation of BEL-7402/5-FU cells and reversed 5-FU resistance in vitro. MEL-pep directly bound to BEL-7402/5-FU cells and disrupted the cell membrane. P-glycoprotein (P-gp) plays an important role in the development of resistance to anticancer drugs. We found that MEL-pep inhibited P-gp expression and increased the intracellular accumulation of the P-gp substrate rhodamine-123 in BEL-7402/5-FU cells. Additionally, the phosphorylation of Akt and NF-κB/p65 nuclear translocation was all inhibited by MEL-pep. Insulin - like growth factor I, a phosphatidylinositol 3 kinase(PI3K) /protein kinase B(AKT) agonist, reversed MEL-pep induced P-gp suppression. Therefore, MEL-pep inhibited P-gp expression by deactivating the PI3K/Akt signaling pathway. Finally, in a BEL-74...
Source: The International Journal of Biochemistry and Cell Biology - Category: Biochemistry Authors: Tags: Int J Biochem Cell Biol Source Type: research