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ORIGINAL RESEARCH article

Front. Pharmacol.
Sec. Pharmacology of Anti-Cancer Drugs
Volume 15 - 2024 | doi: 10.3389/fphar.2024.1367417
This article is part of the Research Topic Innovative Approaches to Overcome Resistance and Toxicities of Anti-Cancer Drugs View all 17 articles

Study on antihepatocellular carcinoma effect of 6-shogaol and curcumin through network-based pharmacological and cellular assay

Provisionally accepted
Qiuxia Jin Qiuxia Jin 1Wenya Jiao Wenya Jiao 1Yunhe Lian Yunhe Lian 2Bimal Chitrakar Bimal Chitrakar 1Yaxin Sang Yaxin Sang 1Xianghong Wang Xianghong Wang 1*
  • 1 Hebei Agricultural University, Baoding, Hebei, China
  • 2 Chenguang Biotechnology Group Co., Ltd., Handan, China

The final, formatted version of the article will be published soon.

    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.Aim: To evaluate the synergistic therapeutic effects of 6-shogaol and curcumin against hepatocellular carcinoma line HepG2 cells.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 were also validated by cellular assays.HepG2 cells were treated with 6-shogaol and curcumin as well as the combination of the two. The combination index (CI) of 6-shogaol and curcumin in HepG2 cells was calculated using Compusyn software according to the Chou-Talalay equation.The synergistic anti-cancer effect was next investigated by MTT assay, apoptosis assay and cell cycle assay. The combined anti-hepatocellular carcinoma effect of the Ras-mediated PI3K/AKT and MAPK signalling pathways was analysed using protein blotting assays.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 down-regulated Cyclin-B, CDK-1, Bcl-2, and up-regulated BAX.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.

    Keywords: 6-shogaol, curcumin, hepatocellular carcinoma, synergistic effect, PI3/AKT signaling pathway, MAPK signaling pathway Abbreviations: BP, biological process, CC, cellular component, CI, cardiac index, DRI, dosereductionindex, FBS, fetal bovine serum, HCC, hepatocellular carcinoma, HPLC, high-performance liquid chromatography, KEGG, Kyoto Encyclopedia of Genes and Genomes

    Received: 08 Jan 2024; Accepted: 26 Jul 2024.

    Copyright: © 2024 Jin, Jiao, Lian, Chitrakar, Sang and Wang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Xianghong Wang, Hebei Agricultural University, Baoding, 071001, Hebei, China

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