Nutrition Research and Practice

The Korean Nutrition Society (한국영양학회)
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Induction of apoptotic cell death in human bladder cancer cells by ethanol extract of Zanthoxylum schinifolium leaf, through ROS-dependent inactivation of the PI3K/Akt signaling pathway

  • Park, Cheol (Division of Basic Sciences, College of Liberal Studies, Dong-eui University) ;
  • Choi, Eun Ok (Anti-Aging Research Center, Dong-eui University) ;
  • Hwangbo, Hyun (Anti-Aging Research Center, Dong-eui University) ;
  • Lee, Hyesook (Anti-Aging Research Center, Dong-eui University) ;
  • Jeong, Jin-Woo (Nakdonggang National Institute of Biological Resources) ;
  • Han, Min Ho (National Marine Biodiversity Institute of Korea) ;
  • Moon, Sung-Kwon (Department of Food and Nutrition, Chung-Ang University) ;
  • Yun, Seok Joong (Department of Urology, College of Medicine, Chungbuk National University) ;
  • Kim, Wun-Jae (Department of Urology, College of Medicine, Chungbuk National University) ;
  • Kim, Gi-Young (Department of Marine Life Science, Jeju National University) ;
  • Hwang, Hye-Jin (Department of Food and Nutrition, College of Nursing, Healthcare Sciences & Human Ecology, Dong-eui University) ;
  • Choi, Yung Hyun (Anti-Aging Research Center, Dong-eui University)
  • Received : 2021.08.25
  • Accepted : 2021.11.23
  • Published : 2022.06.01
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Abstract

BACKGROUND/OBJECTIVES: Zanthoxylum schinifolium is traditionally used as a spice for cooking in East Asian countries. This study was undertaken to evaluate the anti-proliferative potential of ethanol extracts of Z. schinifolium leaves (EEZS) against human bladder cancer T24 cells. MATERIALS/METHODS: Subsequent to measuring the cytotoxicity of EEZS, the anti-cancer activity was measured by assessing apoptosis induction, reactive oxygen species (ROS) generation, and mitochondrial membrane potential (MMP). In addition, we determined the underlying mechanism of EEZS-induced apoptosis through various assays, including Western blot analysis. RESULTS: EEZS treatment concentration-dependently inhibited T24 cell survival, which is associated with apoptosis induction. Exposure to EEZS induced the expression of Fas and Fas-ligand, activated caspases, and subsequently resulted to cleavage of poly (ADP-ribose) polymerase. EEZS also enhanced the expression of cytochrome c in the cytoplasm by suppressing MMP, following increase in the ratio of Bax:Bcl-2 expression and truncation of Bid. However, EEZS-mediated growth inhibition and apoptosis were significantly diminished by a pan-caspase inhibitor. Moreover, EEZS inhibited activation of the phosphoinositide 3-kinase (PI3K)/Akt pathway, and the apoptosis-inducing potential of EEZS was promoted in the presence of PI3K/Akt inhibitor. In addition, EEZS enhanced the production of ROS, whereas N-acetyl cysteine (NAC), a ROS scavenger, markedly suppressed growth inhibition and inactivation of the PI3K/Akt signaling pathway induced by EEZS. Furthermore, NAC significantly attenuated the EEZS-induced apoptosis and reduction of cell viability. CONCLUSIONS: Taken together, our results indicate that exposure to EEZS exhibits anti-cancer activity in T24 bladder cancer cells through ROS-dependent induction of apoptosis and inactivation of the PI3K/Akt signaling pathway.

Keywords

Acknowledgement

This work was supported by the National Research Foundation of Korea Grant (NRF-2020R1A2C1099910) and Korea Basic Science Institute Grant funded (NRF-2020R1A6C101A201).

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