Genistein enhances TRAIL-induced apoptosis through inhibition of p38 MAPK signaling in human hepatocellular carcinoma Hep3B cells
- Authors
- Jin, Cheng-Yun; Park, Cheol; Kim, Gi-Young; Lee, Su-Jae; Kim, Wun-Jae; Choi, Yung Hyun
- Issue Date
- Jul-2009
- Publisher
- ELSEVIER IRELAND LTD
- Keywords
- Genistein; TRAIL; Apoptosis; p38 MAPK
- Citation
- CHEMICO-BIOLOGICAL INTERACTIONS, v.180, no.2, pp.143 - 150
- Indexed
- SCIE
SCOPUS
- Journal Title
- CHEMICO-BIOLOGICAL INTERACTIONS
- Volume
- 180
- Number
- 2
- Start Page
- 143
- End Page
- 150
- URI
- https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/176592
- DOI
- 10.1016/j.cbi.2009.03.020
- ISSN
- 0009-2797
- Abstract
- The cytotoxic effect of the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is limited in some carcinoma cancer cells. However, it was found that treatment with TRAIL in combination with nontoxic concentrations of genistein sensitized TRAIL-resistant human hepatocellular carcinoma Hep3B cells to TRAIL-mediated apoptosis. Combined treatment with genistein and TRAIL-induced chromatin condensation and sub-G1 phase DNA content. These indicators of apoptosis were correlated with the induction of caspase activity that resulted in the cleavage of poly(ADP-ribose) polymerase (PARP). Both cell viability and the cleavage of PARP induced by combined treatment were significantly inhibited by caspase-3, -8 and -9 inhibitors, which demonstrates the important roles of caspases in the observed cytotoxic effects. Genistein treatment also triggered the inhibition of p38-beta mitogen-activated protein kinase (MAPK) activation. Pretreatment with SB203580 resulted in significantly increased sub-G1 population and loss of mitochondrial membrane potential (MMP) in TRAIL-induced apoptosis. By contrast, overexpression of p38 MAPK protected apoptosis by co-treatment with genistein and TRAIL, suggesting that the p38 MAPK act as key regulators of apoptosis in response to treatment with a combination of genistein and TRAIL in human hepatocellular carcinoma Hep3B cells.
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