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The effect of natural polyphenols Resveratrol, Gallic acid, and Kuromanin chloride on human telomerase reverse transcriptase (hTERT) expression in HepG2 hepatocellular carcinoma: role of SIRT1/Nrf2 signaling pathway and oxidative stress

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Abstract

Background

There is evidence that low doses or physiological concentrations of certain natural polyphenols enhance the activity of telomerase. However, the precise mechanism by which natural polyphenols regulate telomerase activity remains unclear. Recent research indicates that NF-E2 related factor 2 (Nrf2) and silent information regulator 1 (SIRT1) are involved in human telomerase reverse transcriptase (hTERT) regulation. Thus, in order to better comprehend the mechanism by which polyphenols regulate hTERT, the present study investigated the effects of the natural polyphenols Resveratrol, Gallic acid, and Kuromanin chloride on hTERT, Nrf2, and SIRT1 expression as well as oxidative stress in HepG2 hepatocellular carcinoma.

Methods

The trypan blue dye exclusion assay was used to assess cell viability. The level of mRNA for hTERT, Nrf2, and SIRT1 was then determined using real-time PCR. A spectrophotometric analysis was conducted to quantify oxidative stress markers.

Results

The results demonstrated that Resveratrol induces the expression of hTERT and the SIRT1/Nrf2 pathway in a dose-dependent manner. Gallic acid at concentrations of 10 and 20 μM also increased the expression of the hTERT and SIRT1/Nrf2 pathway. Furthermore, dose-dependent overexpression of hTERT and Nrf2 was induced by Kuromanin chloride at 10 and 20 µM. Moreover, we found that Resveratrol and Kuromanin chloride ameliorated oxidative stress, whereas Gallic acid exacerbated it.

Conclusions

This study demonstrates that low doses of polyphenols (Resveratrol, Gallic acid, and Kuromanin chloride) upregulate the expression of the hTERT gene in the HepG2 hepatocellular carcinoma cell line, possibly via induction of the SIRT1/Nrf2 signaling pathway. Therefore, by targeting this pathway or hTERT, the anti-cancer effect of polyphenols can be enhanced.

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Data availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

This work was supported by the Behbahan Faculty of Medical Sciences (Grant No. 414). The cooperation of the Department of Biochemistry, Faculty of Medicine, Shiraz University of Medical Sciences is acknowledged.

Funding

This work was supported by the Behbahan Faculty of Medical Sciences (Grant No. 414).

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Authors and Affiliations

  1. Department of Biochemistry, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran

    Delaram Moghadam & Reza Zarei

  2. Infertility Research Center, Shiraz University of Medical Sciences, Shiraz, Iran

    Sina Vakili

  3. Department of Bacteriology and Virology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran

    Rozita Ghojoghi

  4. Behbahan Faculty of Medical Sciences, Behbahan, Iran

    Vahid Zarezade, Ali Veisi, Mohamad Sabaghan, Omid Azadbakht & Hamid Behrouj

  5. Department of Clinical Biochemistry, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran

    Vahid Zarezade

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Contributions

All authors contributed to the study's conception and design. Material preparation, methodology, data collection, data analyses, and writing- original draft preparation were performed by DM, RZ, RGH, and SV. Methodology, conceptualization, data curation, interpretation of the experimental findings, writing-reviewing, and editing were performed by AV, MS, OA, VZ, and HB. All authors read and approved the final version of the manuscript.

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Correspondence to Hamid Behrouj.

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Moghadam, D., Zarei, R., Vakili, S. et al. The effect of natural polyphenols Resveratrol, Gallic acid, and Kuromanin chloride on human telomerase reverse transcriptase (hTERT) expression in HepG2 hepatocellular carcinoma: role of SIRT1/Nrf2 signaling pathway and oxidative stress. Mol Biol Rep 50, 77–84 (2023). https://doi.org/10.1007/s11033-022-08031-7

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