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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 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 downregulated Cyclin-B, CDK-1, Bcl-2, and upregulated 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.
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http://dx.doi.org/10.3389/fphar.2024.1367417 | DOI Listing |
Biomolecules
March 2025
National Centre for Naturopathic Medicine, Faculty of Health, Southern Cross University, Military Road, Lismore, NSW 2480, Australia.
Natural plant products have been used for cancer treatment since ancient times and continue to play a vital role in modern anticancer drug development. However, only a small fraction of identified medicinal plants has been thoroughly investigated, particularly for their effects on cellular pathways in lung and colorectal cancers, two under-researched cancers with poor prognostic outcomes (lung cancers). This review focuses on the lung and colorectal cancer signaling pathways modulated by bioactive compounds from eleven traditional medicinal plants: , , , , , , , , , , and .
View Article and Find Full Text PDFBMC Complement Med Ther
February 2025
Department of Medical Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai, 50200, Thailand.
Background: Leukemic stem cells (LSCs) present a significant challenge in the treatment of leukemia in patients because they exhibit a drug-resistant phenotype, making them difficult to eliminate. Searching for a new anticancer drug is crucial for improving leukemia treatment. Plants from the Zingiberaceae family are frequently used in traditional medicines due to their safety and accessibility.
View Article and Find Full Text PDFJ Agric Food Chem
March 2025
Guangdong Provincial Key Laboratory of Nutraceuticals and Functional Foods, College of Food Science, South China Agricultural University, Guangzhou 510642, China.
Natural spices have gained much attention for their aromatic and pungent flavors as well as their multiple beneficial health effects. As complex organelles that play a central role in energy production, stress response control, cell signal transduction, and metabolism regulation, mitochondria could be regulated by many bioactive components in spices. In this review, the role of mitochondria in maintaining cellular and metabolism homeostasis is summarized.
View Article and Find Full Text PDFInt J Biol Macromol
March 2025
Department of Plantation Products, Spices & Flavour Technology, CSIR-Central Food Technological Research Institute, Mysore 570020, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India. Electronic address:
The synthesis of bioconjugates of curcumin, zingerone, and [6]-shogaol with low molecular weight chitosan (LMWC) is presented. The unconjugated forms of these compounds exhibit low water solubility, poor stability, limited bioavailability, and low target specificity, whereas the synthetic conjugates demonstrate improved physical properties. The synthesis was achieved by forming succinates & then reacting with LMWC.
View Article and Find Full Text PDFPLoS One
November 2024
Pharmacology Unit, Faculty of Medicine and Defence Health, National Defence University of Malaysia, Kuala Lumpur, Malaysia.