Diallyl trisulfide induces pro-apoptotic autophagy via the AMPK/SIRT1 signalling pathway in human hepatocellular carcinoma HepG2 cell line

  • Shuoshuo Sun Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, China
  • Xiyu Liu Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, China
  • Xiao Wei Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, China
  • Shaohong Zhang Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, China; and The Affiliated Huaian NO. 1 People’s Hospital, Nanjing Medical University, Huaian, China
  • Weimin Wang The Affiliated Huaian NO. 1 People’s Hospital, Nanjing Medical University, Huaian, China
Keywords: HepG2 cells, diallyl trisulfide, allicin; apoptosis, autophagy

Abstract

Background: Liver cancer is associated with a high mortality rate worldwide. Hepatocellular carcinoma (HCC) constitutes a large proportion of primary liver cancers, and most of its alterations currently remain untreatable. Diallyl trisulfide (DATS), the main chemical constituent of allicin, affects tumour development by regulating cell apoptosis. Allicin-induced autophagy could contribute to apoptosis in HepG2 cells. We rigorously examined the autophagy-related mechanism of allicin-induced apoptosis in HepG2 cells. We treated HepG2 cells with DATS to explore the effect of DATS on pro-apoptotic autophagy in HepG2 cell lines and examine its specific molecular mechanism.

Methods: HepG2 cells were treated with various concentrations of DATS for 24 and 48 h. Subsequently, cell viability was measured using the cell counting kit-8 (CCK-8) assay and cell clone formation assay. The HepG2 cell apoptosis was measured using Hoechst 33258 staining and western blotting. Autophagy and the AMP-activated protein kinase (AMPK)/NAD-dependent deacetylase sirtuin-1 (SIRT1) signalling pathway were detected using western blotting.

Results: Our results indicated that DATS inhibited HepG2 cell growth. Moreover, the ability of DATS to promote apoptosis in HepG2 cells increased with increasing concentration. We verified the phenomenon of DATS-induced autophagy in HepG2 cells and demonstrated that DATS treatment upregulated the protein expression of LC3-II/I. By measuring the expression of potential autophagy stimulators, we documented that DATS could induce pro-apoptotic autophagy by activating the AMPK/SIRT1 signalling pathway.

Conclusion: DATS induced pro-apoptotic autophagy via the AMPK/SIRT1 signalling pathway in the human HCC HepG2 cell line. Our findings further implicate allicin as a potential therapeutic agent against liver tumours in clinical settings, providing a basis for combining allicin with an autophagy agonist for treating liver cancer.

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Published
2023-05-19
How to Cite
Sun S., Liu X., Wei X., Zhang S., & Wang W. (2023). Diallyl trisulfide induces pro-apoptotic autophagy via the AMPK/SIRT1 signalling pathway in human hepatocellular carcinoma HepG2 cell line. Food & Nutrition Research, 67. https://doi.org/10.29219/fnr.v67.8981
Section
Original Articles