Methyl Palmitate-A suitable adjuvant for Sorafenib therapy to reduce in vivo toxicity and to enhance anti-cancer effects on hepatocellular carcinoma cells.

Abstract

This study focused on evaluating the potency of Methyl Palmitate in reducing in vivo toxicity with enhancement of anti-cancer effects of Sorafenib. In vitro anti-cancer effects on human Hep-G2 cell line were analysed by MTT, Trypan blue, clonogenic, wound scratch migration and TUNEL assays. An in vivo study for anti-angiogenesis effect, toxicity and teratogenicity was analysed in Zebrafish embryos. The combination of Sorafenib (4.5µmol/L) with Methyl Palmitate (3mmol/L) significantly enhanced anti-cancer effects on Hep-G2 cell line by increasing cytotoxicity (P≤.05 in MTT assay; P≤.01 in Trypan blue assay), apoptosis (P≤.05) and decreasing the metastatic migration (P≤.01) than Sorafenib alone treatment. A prominent inhibition of angiogenesis in vivo was observed for combination treatment. At 5dpf, only <20% toxicity was observed for 3mmol/L Methyl palmitate while it was 65.75% for Sorafenib treatment which implies that it is a safer dose for in vivo treatments. A highly significant (P≤.001) reduction (43.20%) in toxicity was observed in combination treatment. Thus, the Sorafenib-Methyl Palmitate combination showed a promising treatment effect with significantly reduced in vivo toxicity when compared with Sorafenib alone treatment, and hence the Methyl Palmitate may serve as a good adjuvant for Sorafenib therapy.