Aim
To evaluate the synergistic therapeutic effects of 6-shogaol and curcumin against hepatocellular carcinoma line HepG2 cells.
Background
Hepatocellular carcinoma currently has the third highest mortality rate in the world. Patients with hepatocellular carcinoma are on the rise and at a younger age, but research into the pharmacological effects of cancer is mostly single-component, and natural plant products can have additive or synergistic effects that can better amplify the effects of intervention in cancer.
Conclusion
6-shogaol and curcumin act synergistically to alter the morphology of hepatocellular carcinoma cells, block the cell cycle in the G2/M phase, inhibit proliferation and division, and effectively promote late apoptosis. The combined action of these two components provides a theoretical basis for the further development of novel anti-liver cancer products.
Methods
In this study, a network pharmacology approach was used to predict and validate the mol ecular targets and pathways of the hepatocellular carcinoma (HCC) of 6-shogaol and curcumin in combination and to investigate their mechanism of action. The
Results
A network pharmacology-based screening identified 72 core targets of 6-curcumin and curcumin in hepatocellular carcinoma, and predicted that the main signalling pathway is the Ras signalling pathway. The anti-cancer effects of 6-shogaol and curcumin were validated in cell-based assays and the optimal synergistic concentrations of 5 μmoL/L for 6-shogaol and 30 μmoL/L for curcumin were determined. 6-shogaol and curcumin synergistically blocked the cell cycle in the G2/M phase and promoted apoptosis. Immunoblot analysis confirmed for the first time the combined action of both in down-regulating the Ras-mediated PI3K/AKT and MAPK signaling pathways. In addition, 6-shogaol and curcumin acting together downregulated Cyclin-B, CDK-1, Bcl-2, and upregulated BAX.