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.

Apoptotic Cell Death via Activation of DNA Degradation, Caspase-3 Activity, and Suppression of Bcl-2 Activity: An Evidence-Based Citrullus colocynthis Cytotoxicity Mechanism toward MCF-7 and A549 Cancer Cell Lines

“…These findings are consistent with earlier studies which reported that phytochemicals like methyl palmitate (which was one of the active principles of C. colocynthis detected in GC-MS in this study) enhanced the anti-cancer effects of Sorafenib therapy by raising cytotoxicity, triggering apoptosis, and preventing Hep-G2 cell migration [49]. Another study concluded that luteolin promoted apoptosis and autophagy in ANA-1 cells most likely by influencing the p38, JNK, and Akt pathways, decreasing Bcl-2 and Beclin-1 activity, and upregulating caspase 8 and caspase 3 expression [74].…”

Comparative Study on the Phytochemical Characterization and Biological Activities of Azolla caroliniana and Azolla filiculoides: In Vitro Study

“…Using GC-MS analysis, several substances with possible anticancer properties have been identified. Long-chain fatty acids and their derivatives have been found in extracts, including octadecadienoic acid [ 37 ], pentadecanoic acid [ 35 ], and methyl palmitate [ 38 ].…”

Uncovering the Key Targets and Therapeutic Mechanisms of Qizhen Capsule in Gastric Cancer through Network Pharmacology and Bioinformatic Analyses

“…By combining various databases as well as biomedical literatures, biomolecular networks can be constructed for a compound [14]. The chemical compounds of QZC were collected from both authoritative databases (TCMSP (https://tcmspw.com/), ETCM (https://www.tcmip.cn/), and TCMID (https://119.3.41.228:8000/tcmid/)) [15] and literatures [16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33]. We used oral bioavailability (OB) and drug-likeness (DL) as indicators to select compounds, and compounds with OB ≥ 30% and DL ≥ 0:18 were selected for further study [34].…”