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

Basic Clin Pharmacol Toxicol. 2021 Mar;128(3):366-378. doi: 10.1111/bcpt.13525. Epub 2020 Nov 17.


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.

Keywords: HEP-G2 cells; Methyl Palmitate; Sorafenib; Zebrafish; anti-angiogenesis and teratogenic.

MeSH terms

  • 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*
  • Palmitates / pharmacology
  • Palmitates / toxicity
  • Sorafenib / administration & dosage*
  • Sorafenib / pharmacology
  • Sorafenib / toxicity
  • Zebrafish


  • Angiogenesis Inhibitors
  • Palmitates
  • Sorafenib
  • methyl palmitate