Toxicological Research

Korean Society of Toxicology & Korea Environmental Mutagen Society (한국독성학회)
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Kaempferol induces apoptosis through the MAPK pathway and regulates JNK-mediated autophagy in MC-3 cells

  • Su‑Ji Jeon (Department of Companion and Laboratory Animal Science, Kongju National University) ;
  • Gi‑Hwan Jung (Department of Companion and Laboratory Animal Science, Kongju National University) ;
  • Eun‑Young Choi (Department of Companion and Laboratory Animal Science, Kongju National University) ;
  • Eun‑Ji Han (Department of Companion and Laboratory Animal Science, Kongju National University) ;
  • Jae‑Han Lee (Department of Companion and Laboratory Animal Science, Kongju National University) ;
  • So‑Hee Han (Department of Companion and Laboratory Animal Science, Kongju National University) ;
  • Joong‑Seok Woo (Department of Companion and Laboratory Animal Science, Kongju National University) ;
  • Soo‑Hyun Jung (Department of Companion and Laboratory Animal Science, Kongju National University) ;
  • Ji‑Youn Jung (Department of Companion and Laboratory Animal Science, Kongju National University)
  • Received : 2023.04.05
  • Accepted : 2023.08.02
  • Published : 2024.01.15
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Abstract

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 kaempferoltreated 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.

Keywords

Acknowledgement

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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