Gambogenic Acid Inhibits Basal Autophagy of Drug-Resistant Hepatoma Cells and Improves Its Sensitivity to Adriamycin

• Published in: Biological & pharmaceutical bulletin Vol. 45; no. 1; pp. 63 - 70
• Main Authors: Wang, Meng, Zhan, Fan, Cheng, Hui, Li, Qinglin
• Format: Journal Article
• Language: English
• Published: Japan The Pharmaceutical Society of Japan 01-01-2022; Pharmaceutical Society of Japan; Japan Science and Technology Agency
• Subjects: Adriamycin (ADM); Apoptosis; Autophagy; BAX protein; Bcl-2 protein; Cell activation; Cell viability; Drug resistance; drug-resistant; Flow cytometry; gambogenic acid; Hepatoma; Liver cancer; Phagosomes; Plant extracts; Protein expression; Proteins; Transmission electron microscopy; Tumors; apoptosis; gambogenic acid; autophagy; drug-resistant; Adriamycin (ADM)
• ISSN: 0918-6158; 1347-5215
• DOI: 10.1248/bpb.b21-00511

Gambogenic acid (GNA) is extracted from plant Gamboge, has a wide range of anti-tumor effects. In this paper, we study the inhibitory effect of GNA on the BEL-7402/ADM of hepatoma resistant cell lines and further study the mechanism of action. Cell viability test represented that GNA could improve the sensitivity of hepatoma drug-resistant cell line BEL-7402/ADM to Adriamycin (ADM), and further study by 4′,6-diamidino-2-phenylindole (DAPI) staining and flow cytometry found that GNA could improve the effect of ADM on promoting apoptosis in BEL-7402/ADM cells, and the activation of apoptosis-related protein was significantly increased, and the ratio of Bax to Bcl-2 was significantly increased. Monodansylcadaverine staining and transmission electron microscopy showed that the basal autophagy level of BEL-7402/ADM cells was higher than that of BEL-7402 cells. Further detection of protein expression found that the intracellular LC3-II to LC3-I ratio and Beclin 1 protein expression increased in the combination of GNA and ADM, but the protein level of p62 increased significantly. GNA inhibit protective autophagy in BEL-7402/ADM cells and promote the role of ADM in inducing apoptosis, thereby increasing ADM sensitivity to BEL-7402/ADM cells, and the effect of GNA inhibition of autophagy may be achieved by inhibiting the degradation of autophagosomes.