Diallyl Sulfide and Its Role in Chronic Diseases Prevention.

Diallyl sulfide (C6H10S, DAS) is one of the novel natural organosulfur compounds, which is mostly obtained from the genus Allium plants. Numerous studies have revealed several unique properties of DAS in terms of its health-promoting effects. DAS has proved to be anticancer, antimicrobial, anti-angiogenic, and immunomodulatory like unique functions as demonstrated by the multiple investigations. Diallyl sulfide can also impede oxidative stress and chronic inflammation as suggested by the literature. Studies also explored that DAS could thwart the development of chronic diseases like cancer, neuronal, cardiovascular disease through modulating mechanistic pathways involved in pathogenesis. In this book chapter, we have attempted to give the comprehensive view on DAS about the physiochemical and biological properties, and its preventive role in chronic diseases with a mechanistic overview.

Resveratrol improves the anticancer effects of doxorubicin in vitro and in vivo models: A mechanistic insight.

BACKGROUND: Resveratrol (RSVL), a well known dietary compound and in combination with doxorubicin (DOX) has gained a global importance for cancer prevention. However, mechanism of action by this combination is not well understood till date. HYPOTHESIS: The synergistic combination of RSVL and DOX might be more effective in anti-cancer activity by modulating the diverse cancer signaling pathways as compared to their alone treatments. METHODS: The cytotoxicity of alone and combination doses of RSVL and DOX were analyzed by colorimetric MTT(3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide) cell proliferation assay. The migration and colony forming abilities were evaluated by wound healing and clonogenic assays. Apoptosis was detected by Annexin V/PI and DAPI stainings. The cell cycle and intracellular reactive oxygen species (ROS) generation were measured by flow cytometry. The differential expression of genes and proteins were measured by qRT-PCR and western blotting analyses. Finally, in-vivo studies were performed in Ehrlich ascitic carcinoma (EAC) mouse model. RESULTS: The synergistic combination of DOX (IC20) and RSVL (IC30) was selected based on the combination index values in MCF-7 and MDA-MB-231 cell lines. This combination showed potent growth inhibition with ∼2.5 fold of dose advantage and also significantly decreased the wound healing and clonogenic potential of breast cancer cells. The combination treatment was also found to inhibit the inflammatory response (NF-kB, COX-2), autophagic flux (LC3, Beclin-1), redox regulation (Nrf2) and induces apoptosis (BAX: BCL-2 ratio and Caspase-9) in breast cancer cells. Further, combined dosages of DOX (5 mg/kg b.wt) and RSVL (10 mg/kg b.wt) inhibited tumor volume with increased life span (139%, p value<0.05) in Ehrlich ascitic carcinoma (EAC) cells bearing mice. CONCLUSION: In brief, our results suggested that resveratrol chemosensitizes doxorubicin in combination, through inhibiting breast cancer cells proliferation and invasion, and inducing apoptosis via suppression of chronic inflammation and autophagy.

Sulfur alleviates arsenic toxicity by reducing its accumulation and modulating proteome, amino acids and thiol metabolism in rice leaves.

Arsenic (As) contamination of water is a global concern and rice consumption is the biggest dietary exposure to human posing carcinogenic risks, predominantly in Asia. Sulfur (S) is involved in di-sulfide linkage in many proteins and plays crucial role in As detoxification. Present study explores role of variable S supply on rice leaf proteome, its inclination towards amino acids (AA) profile and non protein thiols under arsenite exposure. Analysis of 282 detected proteins on 2-DE gel revealed 113 differentially expressed proteins, out of which 80 were identified by MALDI-TOF-TOF. The identified proteins were mostly involved in glycolysis, TCA cycle, AA biosynthesis, photosynthesis, protein metabolism, stress and energy metabolism. Among these, glycolytic enzymes play a major role in AA biosynthesis that leads to change in AAs profiling. Proteins of glycolytic pathway, photosynthesis and energy metabolism were also validated by western blot analysis. Conclusively S supplementation reduced the As accumulation in shoot positively skewed thiol metabolism and glycolysis towards AA accumulation under AsIII stress.