Effect of diallyl disulfide on insulin-like growth factor signaling molecules involved in cell survival and proliferation of human prostate cancer cells in vitro and in silico approach through docking analysis

Purpose: Diallyl Disulfide (DADS) is one of the major components of garlic, which inhibits the proliferation of various cancer cells. Our previous studies showed that DADS inhibits cell growth and induces apoptosis on prostate cancer cells. Insulin like growth factor signaling pathway plays a significant role on prostate cancer cell growth and survival and it's over expression also identified in human prostate cancers. The molecular mechanism of ICE mediated PI3K/Akt signaling remains to be elucidated. The present study was designed to evaluate the effects of diallyl disulfide on IGF signaling in androgen independent prostate cancer cells (PC-3). Methods: DADS (10-50 mu M) caused dose-dependent inhibition of PC-3 cells, were analyzed by MTF. IG50 value of PC-3 cells was 40 mu M for 24 h. Interestingly, DADS also altered the mRNA and protein expressions of IGF signaling and apoptotic molecules which were confirmed by semi quantitative PCR and western blot method. Further the docking study of DADS with ICE receptor was carried out by Ligand Fit of Discovery studio. Accord Excel Package was used for the prediction of ADME properties of the compound. Results: The results suggests that DADS decreases the survival rate of androgen independent prostate cancer cells by modulating the expression of IGF system, which leads to inhibition of phosphorylation of Akt, thereby inhibits cell cycle progression and survival by lowering the expression of cyclin D1, NFkB and anti-apoptotic Bcl-2 molecule and increasing the level of pro-apoptotic (Bad and Bax) signaling molecules which leads to apoptosis. Conclusion: The present investigation showed downregulation of Akt and a concomitant increase in apoptosis in DADS treated prostate cancer cells. Since inhibition of this Akt pathway by DADS leads to inhibition in cancer cell progression, it is highly suggested that DADS has the potential use as a therapy for prostate cancer. (C) 2012 Elsevier GmbH. All rights reserved.