Research Articles

2-hydroxy-3-methyl anthraquinone promotes apoptosis and inhibits invasion of human hepatocellular carcinoma cells by targeting nicotinamide adenine dinucleotide-dependent protein deacetylase sirtuin-1/cellular tumor antigen p53 signaling pathway

  • Shuang WU ,
  • Qiao LI ,
  • Xieying ZHU ,
  • Taoyuan ZHANG
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  • 1 Clinical Laboratory, Affiliated Children Hospital of Xi’an Jiaotong University, Xian 710003, China
    2 Department of Anesthesiology, Rizhao International Heart Hospital, Rizhao 276800, China

Received date: 2023-01-22

  Accepted date: 2023-04-23

  Online published: 2023-09-04

Supported by

Natural Science Basic Research Plan in Shannxi Province of China, the Intervention and Mechanism of Developmenta-lendotheliallocus-1 Regulating Macrophage Efferocytosis on Airway Inflammation in Chronic Obstructive Pulmonary Disease(2020JQ-543);Function and Mechanism of New Tumor Suppressor TSC22D2 in Cancer Glycometabolism(2020JQ-927);Fundamental Research Funds for The Central University: the Role of TSC22D2-centered Protein Interaction Map in Cancer Glycometabolism and Cell Growth(xzy012019129)

Abstract

OBJECTIVE: To investigate the anti-liver cancer effect of 2-hydroxy-3-methyl anthraquinone (HMA) and the specific mechanism based on nicotinamide adenine dinucleotide-dependent protein deacetylase sirtuin-1 (SIRT1)/cellular tumor antigen p53 (p53) pathway.

METHODS: Cell counting kit-8 method was used to observe the effect of HMA on the activity of human hepatocellular carcinoma cells (HepG2) cells. At 72 h and 80 μL HMA, the apoptosis rate of HepG2 cells in each group was measured by flow cytometry. Transwell was used to assay for cell invasion. The protein expression levels of SIRT1, p53, B-cell lymphoma-2 (Bcl-2), Bcl-2 associated X protein (Bax), caspase-9 (CASP9) and caspase-3 (CASP3) were detected by Western Blot.

RESULTS: HMA significantly inhibited the proliferation of HepG2 cells, The half inhibiting concentration (IC50) of the HMA at 24, 48 and 72 h were examined and it were 126.3, 98.6, and 80.55 μM, respectively. Compared with the control group, the apoptosis rate of HMA, Selisistat (EX527), and HMA+ EX527 groups enhanced, while the apoptosis rate of SRT1720 diminished, demonstrating that inhibition of SIRT1 can lead to apoptosis of HepG2 cells. HMA+ EX527 group had the highest apoptosis rate, the lowest expression of SIRT1 and Bcl-2, and the highest expression of p53, Bax, CASP9 and CASP3. The number of invasions of HepG2 was significantly reduced after HMA and EX527 intervened. Western blot shows HMA could inhibit SIRT1, promote the expression of p53, and decrease the ratio of Bcl-2/Bax.

CONCLUSIONS: HMA induced apoptosis in HepG2 cells, while inhibiting proliferation and invasion. The mechanism of HMA against HCC may be related to the SIRT1/p53 pathway.

Cite this article

Shuang WU , Qiao LI , Xieying ZHU , Taoyuan ZHANG . 2-hydroxy-3-methyl anthraquinone promotes apoptosis and inhibits invasion of human hepatocellular carcinoma cells by targeting nicotinamide adenine dinucleotide-dependent protein deacetylase sirtuin-1/cellular tumor antigen p53 signaling pathway[J]. Journal of Traditional Chinese Medicine, 2024 , 44(6) : 1104 -1110 . DOI: 10.19852/j.cnki.jtcm.20230904.005

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