Brucea javanica oil inhibits proliferation of hepatocellular carcinoma cells and induces apoptosis via the PI3K/AKT pathway

• Main Authors: Yan-Peng Du, Zhan Ye, Zhao-Jun Zheng, You-Dong, Jing Chen, Farah Zaaboul, Yong-Jiang Xu, Yuan-Fa Liu
• Format: Article
• Language: English
• Published: Hong Kong Gold Orchid Science and Technology Co., Limited 2021-03-01
• Series: Traditional Medicine Research
• Subjects: brucea javanica oil; hepatocellular carcinoma; hepg2 cell; cell proliferation; cell apoptosis; pi3k/akt
• Online Access: https://www.tmrjournals.com/article.html?J_num=1&a_id=1187

Background: Brucea javanica oil (BJO), distributed primarily in Southeast Asia, has long been utilized as a therapeutic agent for treating malignancies. However, its anticancer mechanisms are not clearly understood. The objective of this study was to examine the mechanisms underlying its treatment of hepatocellular carcinoma cells. Methods: CCK8 assay was used to evaluate cell viability. Hoechst33342 staining and flow cytometry analyses were used to examine apoptosis. Mito-Tracker Red CMXRos kit was used to measure the membrane potential of mitochondria. ATP assay kit was used to evaluate ATP levels. Western blots were used to assess the presence of AKT, adenosine monophosphate-activated protein kinase, Caspase3, Caspase9, Bax, and Bcl-2. Results: BJO inhibited the proliferation of hepatocellular carcinoma cells HepG2 in a time- and dose-dependent manner. It induced apoptosis, with the percentage of cells treated with 50-150 μg/mL BJO increasing from 8.01% to 28.02% in a concentration-dependent manner (P < 0.05, when 50 μg/mL of BJO group compared with the control group; P < 0.001, when 100 or 150 μg/mL of BJO group compared with the control group). After exposed to BJO, the expression of C-caspase3, C-caspase9 and Bax upregulated while that of Bcl-2 downregulated. BJO suppressed the PI3K/AKT pathway and promoted phosphorylation of adenosine monophosphate-activated protein kinase, while repressing the phosphorylation of mechanistic target of rapamycin. Compared with treatment by BJO alone, the PI3K/AKT agonist 740Y-P increased the survival rate of HepG2 cells (P < 0.01) and attenuated the inhibitory effect of BJO on cell apoptosis (P < 0.05). Conclusion: BJO is capable of inhibiting proliferation of HepG2 cells and inducing apoptosis via the PI3K/AKT pathway.