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Etoposide induces a mixed type of programmed cell death and overcomes the resistance conferred by Bcl-2 in Hep3B hepatoma cells

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Author(s)
SEUNG HEE YOOYOUNG GEOL YOONJEE SUK LEEYEON SUK SONGJOON SEOK OHBONG SOO PARKTAEG KYU KWONCHEOL PARKYUNG HYUN CHOIYOUNG HYUN YOO
Keimyung Author(s)
Kwon, Taeg Kyu
Department
Dept. of Immunology (면역학)
Journal Title
International Journal of Oncology
Issued Date
2012
Volume
41
Issue
4
Abstract
. The Bcl-2 protein is known to exert not only anti-apoptotic but also anti-autophagic activities. Numerous studies have demonstrated that etoposide, which is one of the most widely used cancer chemotherapy agents, induces apoptotic cell death. However, the exact molecular mechanism leading to cell death by etoposide remains to be resolved. This study aimed to dissect the mode of cell death induced by etoposide in Hep3B hepatoma cells. Furthermore, this study was conducted to examine whether etoposide overcomes the resistance conferred by Bcl-2 in Hep3B hepatoma cells. We observed that Hep3B cells treated with etoposide show not only apoptotic but autophagic phenotypes. Autophagy inhibition by 3-methyladenine (3MA) and caspase inhibition by zVAD-fmk effectively decreased autophagic and apoptotic phenotypes, respectively. However, either zVAD-fmk or 3MA only partially prevented cell death. These data indicate that etoposide concomitantly induces autophagic cell death and apoptosis in Hep3B cells. Importantly, etoposide can effectively induce cell death in Bcl-2-overexpressing Hep3B cells. Conversely, staurosporine, which exclusively induces apoptosis in Hep3B cells, did not efficiently induce cell death in Bcl‑2‑overexpressing Hep3B cells. Staurosporine-treated Hep3B cells also showed an autophagic phenotype. While autophagy is cell death-inducing in Hep3B cells treated with etoposide, it is cytoprotective in Hep3B cells treated with staurosporine. To this end, we observed that etoposide-induced mixed type of programmed cell death is associated with the dissociation of Bcl-2 from Beclin-1. Taken together, etoposide induces a mixed type of programmed cell death and overcomes the resistance conferred by Bcl-2 in Hep3B hepatoma cells
Keimyung Author(s)(Kor)
권택규
Publisher
School of Medicine
Citation
SEUNG HEE YOO et al. (2012). Etoposide induces a mixed type of programmed cell death
and overcomes the resistance conferred by Bcl-2 in Hep3B hepatoma cells. International Journal of Oncology, 41(4), 1443–1454. doi: 10.3892/ijo.2012.1585
Type
Article
ISSN
1019-6439
Source
http://www.spandidos-publications.com/ijo/41/4/1443
DOI
10.3892/ijo.2012.1585
URI
https://kumel.medlib.dsmc.or.kr/handle/2015.oak/36004
Appears in Collections:
1. School of Medicine (의과대학) > Dept. of Immunology (면역학)
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