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Kaempferol induces apoptosis through the MAPK pathway and regulates JNK-mediated autophagy in MC-3 cells

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This study sought to determine the anticancer effect of kaempferol, a glycone-type flavonoid glycoside with various pharmacological benefits, on human oral cancer MC-3 cells. In vitro studies comprised a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, annexin V and propidium iodide staining, western blotting analysis, and acridine orange staining, while the in vivo studies entailed a xenograft model, hematoxylin and eosin staining, and TdT-mediated dUTP-biotin nick end labelling. In vitro, kaempferol reduced the rate of survival of MC-3 cells, mediated intrinsic apoptosis, increased the number of acidic vesicular organelles, and altered the expression of autophagy-related proteins. Further, treatment with the autophagy inhibitors revealed that the induced autophagy had a cytoprotective effect on apoptosis in kaempferol-treated MC-3 cells. Kaempferol also decreased the expression of phosphorylated extracellular signal-regulated kinase and increased that of phosphorylated c-Jun N-terminal kinase (p-JNK) and phosphorylated p38 kinase in MC-3 cells, suggesting the occurrence of mitogen-activated protein kinase-mediated apoptosis and JNK-mediated autophagy. In vivo, kaempferol reduced tumor growth inducing apoptosis and autophagy. These results showed that kaempferol has the potential use as an adjunctive agent in treating oral cancer.

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Data availability

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

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Funding

This study was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (2021R1A2C1010912).

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Authors and Affiliations

  1. Department of Companion and Laboratory Animal Science, Kongju National University, Daehak-ro, Yesan-eup, Yesan-gun, Chungcheongnam-do, 32439, Republic of Korea

    Su-Ji Jeon, Gi-Hwan Jung, Eun-Young Choi, Eun-Ji Han, Jae-Han Lee, So-Hee Han, Joong-Seok Woo, Soo-Hyun Jung & Ji-Youn Jung

  2. Research Institute for Natural Products, Kongju National University, Daehak-ro, Yesan-eup, Yesan-gun, Chungcheongnam-do, 32439, Republic of Korea

    Ji-Youn Jung

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Contributions

SJJ and JHL designed the study and contributed the experiments. JSW, SHH and EYC contributed to data analysis. SJJ and GHJ contributed material preparation. EJH, JSW and SHJ contributed supervision present study. SJJ, GHJ contributed original manuscript writing. JYJ contributed to the manuscript review and editing, Funding acquisition, product administration. All authors approved the publication of this version of the manuscript and agreed to be accountable for all aspects of the work.

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Correspondence to Ji-Youn Jung.

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This study was approved by the Institutional Animal Care and Use Committee of Kongju University (KNI_2021-06, Chungcheongnam-do, Korea) and was conducted in compliance with committee guidelines.

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Jeon, SJ., Jung, GH., Choi, EY. et al. Kaempferol induces apoptosis through the MAPK pathway and regulates JNK-mediated autophagy in MC-3 cells. Toxicol Res. 40, 45–55 (2024). https://doi.org/10.1007/s43188-023-00206-z

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