RESUMO
Diallyl disulfide (DADS) is a major organo-sulfur compound derived from garlic (Allium sativum), which inhibits the proliferation of various types of cancer cells. In this study we investigated the effect of DADS on the induction of apoptosis, as well as its regulatory effect on the activation of transcription factors in B16F-10 melanoma cells. Treatment of B16F-10 cells with nontoxic concentrations of DADS resulted in the presence of apoptotic bodies and induced DNA fragmentation in a dose-dependent manner. Cell-cycle analysis revealed that the occurrence of the sub-G1 peak was significantly elevated in DADS-treated cells. DADS treatment also down-reguated Bcl-2 expression and up-regulated p53, caspase-9, and caspase-3 expression in B16F-10 melanoma cells. The study also reveals that DADS inhibited the activation and nuclear translocation of p65, p50, and c-Rel subunits of nuclear factor (NF)-B and other transcription factors, such as c-fos, activated transcription factor-2, and cyclic adenosine monophosphate response element-binding protein, in B16F-10 melanoma cells The pro-inflammatory cytokine production and gene expression of tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, IL-6, and granulocyte-macrophage colony-stimulating factor (GM-CSF) were down-regulated in DADS-treated cells compared with control B16F-10 metastatic melanoma cells. DADS induces caspase-dependent apoptosis through a mitochondria-mediated intrinsic pathway in B16F-10 melanoma cells by activating p53 and caspase-3 gene expression and suppressing pro-inflammatory cytokines and NF-B-mediated Bcl-2 activation.
