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 pathwayopen access
- Authors
- Park, Cheol; Choi, Eun Ok; Hwangbo, Hyun; Lee, Hyesook; Jeong, Jin-Woo; Han, Min Ho; Moon, Sung-Kwon; Yun, Seok Joong; Kim, Wun-Jae; Kim, Gi-Young; Hwang, Hye-Jin; Choi, Yung Hyun
- Issue Date
- Jun-2022
- Publisher
- 한국영양학회
- Keywords
- Apoptosis; reactive oxygen species; caspases; mitochondria; cytochrome epsilon
- Citation
- Nutrition Research and Practice, v.16, no.3, pp 330 - 343
- Pages
- 14
- Journal Title
- Nutrition Research and Practice
- Volume
- 16
- Number
- 3
- Start Page
- 330
- End Page
- 343
- URI
- https://scholarworks.bwise.kr/cau/handle/2019.sw.cau/58264
- DOI
- 10.4162/nrp.2022.16.3.330
- ISSN
- 1976-1457
2005-6168
- 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.
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