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 (4.5 µmol/L) with Methyl Palmitate (3 mmol/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 5 dpf, only <20% toxicity was observed for 3 mmol/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.

• Authors: Raja David Isac Evangeline Breeta, Viswanathan Mariammal Berlin Grace, Devarajan David Wilson
• Journal: Basic & clinical pharmacology & toxicology (Basic Clin Pharmacol Toxicol) Vol. 128 Issue 3 Pg. 366-378 (Mar 2021) ISSN: 1742-7843 [Electronic] England
• PMID: 33128309 (Publication Type: Journal Article)
• Copyright: © 2020 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

Chemical References

• Angiogenesis Inhibitors
• Palmitates
• Sorafenib
• methyl palmitate

Topics

• Abnormalities, Drug-Induced (etiology)
• Angiogenesis Inhibitors (pharmacology)
• Animals
• Antineoplastic Combined Chemotherapy Protocols (pharmacology)
• Apoptosis (drug effects)
• Carcinoma, Hepatocellular (drug therapy)
• Cell Movement (drug effects)
• Hep G2 Cells
• Humans
• Liver Neoplasms (drug therapy)
• Palmitates (administration & dosage, pharmacology, toxicity)
• Sorafenib (administration & dosage, pharmacology, toxicity)
• Zebrafish