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Apoptosis Induction of Human Prostate Carcinoma DU145 Cells by Diallyl Disulfide via Modulation of JNK and PI3K/AKT Signaling Pathways
Dongnam Institute of Radiological & Medicine Sciences, Busan 619-953, Korea
Laboratory of Immunobiology, Department of Marine Life Sciences, Jeju National University, Jeju 690-756, Korea
Biotechnology Examination Division, Chemistry and Biotechnology Examination Bureau, Korean Intellectual Property Office, Daejeon 302-701, Korea
Division of Meridian and Structural Medicine, School of Korean Medicine, Pusan National University, Yangsan 626-870, Korea
Department of Anatomy and Cell Biology and Mitochondria Hub Regulation Center, College of Medicine, Dong-A University, Busan 602-714, Korea
Department of Biochemistry, College of Oriental Medicine and Anti-Aging Research Center, Dongeui University, Busan 614-052, Korea
* Author to whom correspondence should be addressed.
Received: 24 September 2012; in revised form: 22 October 2012 / Accepted: 26 October 2012 / Published: 2 November 2012
Abstract: Diallyl disulfide (DADS), a sulfur compound derived from garlic, has various biological properties, such as anticancer, antiangiogenic and anti-inflammatory effects. However, the mechanisms of action underlying the compound's anticancer activity have not been fully elucidated. In this study, the apoptotic effects of DADS were investigated in DU145 human prostate carcinoma cells. Our results showed that DADS markedly inhibited the growth of the DU145 cells by induction of apoptosis. Apoptosis was accompanied by modulation of Bcl-2 and inhibitor of apoptosis protein (IAP) family proteins, depolarization of the mitochondrial membrane potential (MMP, ΔΨm) and proteolytic activation of caspases. We also found that the expression of death-receptor 4 (DR4) and Fas ligand (FasL) proteins was increased and that the level of intact Bid proteins was down-regulated by DADS. Moreover, treatment with DADS induced phosphorylation of mitogen-activated protein kinases (MAPKs), including extracellular-signal regulating kinase (ERK), p38 MAPK and c-Jun N-terminal kinase (JNK). A specific JNK inhibitor, SP600125, significantly blocked DADS-induced-apoptosis, whereas inhibitors of the ERK (PD98059) and p38 MAPK (SB203580) had no effect. The induction of apoptosis was also accompanied by inactivation of phosphatidylinositol 3-kinase (PI3K)/Akt and the PI3K inhibitor LY29004 significantly increased DADS-induced cell death. These findings provide evidence demonstrating that the proapoptotic effect of DADS is mediated through the activation of JNK and the inhibition of the PI3K/Akt signaling pathway in DU145 cells.
Keywords: diallyl disulfide; apoptosis; MAPK; PI3K/Akt
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Shin, D.Y.; Kim, G.-Y.; Lee, J.H.; Choi, B.T.; Yoo, Y.H.; Choi, Y.H. Apoptosis Induction of Human Prostate Carcinoma DU145 Cells by Diallyl Disulfide via Modulation of JNK and PI3K/AKT Signaling Pathways. Int. J. Mol. Sci. 2012, 13, 14158-14171.
Shin DY, Kim G-Y, Lee JH, Choi BT, Yoo YH, Choi YH. Apoptosis Induction of Human Prostate Carcinoma DU145 Cells by Diallyl Disulfide via Modulation of JNK and PI3K/AKT Signaling Pathways. International Journal of Molecular Sciences. 2012; 13(11):14158-14171.
Shin, Dong Y.; Kim, Gi-Young; Lee, Jun H.; Choi, Byung T.; Yoo, Young H.; Choi, Yung H. 2012. "Apoptosis Induction of Human Prostate Carcinoma DU145 Cells by Diallyl Disulfide via Modulation of JNK and PI3K/AKT Signaling Pathways." Int. J. Mol. Sci. 13, no. 11: 14158-14171.