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Methyl Palmitate—A suitable adjuvant for Sorafenib therapy to reduce in vivo toxicity and to enhance anti‐cancer effects on hepatocellular carcinoma cells
Author(s) -
Breeta Raja David Isac Evangeline,
Grace Viswanathan Mariammal Berlin,
Wilson Devarajan David
Publication year - 2021
Publication title -
basic and clinical pharmacology and toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.805
H-Index - 90
eISSN - 1742-7843
pISSN - 1742-7835
DOI - 10.1111/bcpt.13525
Subject(s) - sorafenib , in vivo , toxicity , pharmacology , angiogenesis , mtt assay , medicine , clonogenic assay , apoptosis , hepatocellular carcinoma , cancer research , chemistry , biology , biochemistry , microbiology and biotechnology
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.