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Molecular docking and in vitro experiments verified that kaempferol induced apoptosis and inhibited human HepG2 cell proliferation by targeting BAX, CDK1, and JUN

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Abstract

Hepatocellular carcinoma, as a common liver cirrhosis complication, has become the sixth most common cancer worldwide, and its increasing incidence has resulted in considerable medical and economic burdens. As a natural polyphenolic compound, kaempferol has exhibits a wide range of antitumor activities against multiple cancer targets. In this study, the Autodock software was used for molecular docking to simulate the interaction process between kaempferol and HCC targets and the PyMOL software was used for visualization. Proliferation of kaempferol HepG2 cells under the effect of kaempferol was detected using Cell Counting Kit-8 (CCK-8) assay, and the apoptosis rate of HepG2 cells was detected using flow cytometry. The expressions of proteins BAX, CDK1, and JUN protein expressions were detected by Western blot. Molecular docking found that the kaempferol ligand has 3 rotatable bonds, 6 nonpolar hydrogen atoms, and 12 aromatic carbon atoms, and can form complexes with the kaempferol targets P53, BAX, AR, CDK1, and JUN through electrostatic energy. GO (Gene Ontology) enrichment analysis suggests that kaempferol regulates the biological function of hepatocellular carcinoma cells and is related to apoptosis. Cell Counting Kit-8 assay suggested that Kaempferol can significantly inhibited HepG2 cell proliferation, and the inhibition rate increased with the increase in drug concentration and incubation time. Moreover, kaempferol can promoted HepG2 cell apoptosis in a dose-dependent manner. This compound upregulated BAX and JUN expression and downregulated CDK1 expression. Thus, Kaempferol can promote HepG2 cell apoptosis, and the regulatory mechanism may be related to the regulation of the expression levels of the apoptosis-related proteins BAX, CDK1, and JUN.

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Acknowledgements

The authors acknowledge the Hebei Provincial Department of Finance [Project (2018) No.674] for financial assistance. They are grateful to the Institute of Oncology, Fourth Hospital of Hebei Medical University for their experimental technical support for this study.

Funding

This study was supported by Hebei Provincial Department of Finance (Project [2018] No. 674).

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Authors and Affiliations

  1. Department of General Medicine, The Fourth Hospital of Hebei Medical University, 12 Health Road, Shijiazhuang, 050011, Hebei, China

    Qin Zhang, Li Chen, Mengxi Gao, Shubin Wang, Lingzhen Meng & Liru Guo

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  1. Qin Zhang
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  2. Li Chen
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  3. Mengxi Gao
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ZQ in is responsible for completing the bioinformatics, experimental operation and thesis writing. CL and GM participate in data collection and provide experimental suggestions, ML provides technical support, and GL provides the overall direction and writing guidance of this research.

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Correspondence to Liru Guo.

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Zhang, Q., Chen, L., Gao, M. et al. Molecular docking and in vitro experiments verified that kaempferol induced apoptosis and inhibited human HepG2 cell proliferation by targeting BAX, CDK1, and JUN. Mol Cell Biochem 478, 767–780 (2023). https://doi.org/10.1007/s11010-022-04546-6

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