NO synthase II, is capable of generating high local intracellular and extracellular concentrations of NO. Under these conditions, NO synthase II is induced in a variety of cells including the intestinal epithelium. During inflammation, intestinal epithelial cells are exposed to cytokines, bacterial products, and many other substances that affect cellular functions. By acting as an antioxidant, inhibiting leukocyte adherence, and maintaining mucosal blood flow. At physiologic concentrations, NO protects the gastrointestinal mucosa from injury. reported that resveratrol might rapidly increase NO production in cultured endothelial cells. Substitution of position 3 with a sugar molecule do as not interfere with scavenger functions of the hydroxi-stilbene (ISBs) that is ascribed in major measure to 4′ OH. In the Resveratrol there are 3 hydroxyl-groups in 3, 4, and 5 position of stilbene scaffold whereas Polydatin has the position 3 is occupied by a glucopiranoside ring. Chemically these molecules are stilbenes derivatives.
#Calcusyn combination index free
Resveratrol (trans-3,5,49-trihydroxystilbene) and its natural precursor Polydatin (resveratrol-3-O-b-mono- D-glucoside Product Origin: Root of Polygonum cuspidatum) are phytoalexins, molecules produced by spermatophytes plants to protect germinal centers, fruits, and roots, by attack by fungi, bacteria or free radicals. The ideal characteristics or chemopreventive/therapeutic agents is the specific modulation of aberrant signalling pathways through the induction of apoptosis. In contrast to normal cells, the basal level of inducible heat shock proteins (HSPs) are frequently higher in tumour cells Phytochemicals are among the most promising chemopreventive and treatment options for the management of cancer. The mechanisms underlying its survival advantage may be related in part to the high endogenous expression of stress proteins. As a consequence, the tumours are hard to treat and often proliferate rapidly, even under conditions that may adversely affect normal cells. Adenocarcinoma cells, such as CRC cells, are remarkably resistant to damage induced by radiation or systemic, immunological and chemotherapeutic agents. Our data suggest the potential use of polydatin in combination chemotherapy for human colon cancer.Ĭolorectal cancer (CRC) remains a leading cause of mortality among many racial and ethnic groups throughout the world. Conclusionsįrom morphological, and biochemical outcome we obtained evidences that polydatin induced a transition from a proliferative morphology to cell-specific differentiated structures and caused human CaCo-2 cell death by induction of apoptosis. Worthy of note treatment with polydatin induced a nuclear localization and decreased expression of heat shock protein 27, and vimentin redistributed within the cell. We demonstrated that polydatin alone or in combination with resveratrol at 3:1 molar ratio synergistically modulated oxidative stress, cell cycle, differentiation and apoptosis. Simultaneous exposure to polydatin and resveratrol produced synergistic antiproliferative effects compared with single compound treatment. We have selected a synergistic combination and we have evaluated its effect on the biological and molecular mechanisms of cell death. The polydatin and resveratrol pharmacological interaction was evaluated in vitro on growing and differentiated Caco-2 cell lines by median drug effect analysis calculating a combination index with CalcuSyn software. In this study, we investigate whether the Resveratrol (trans-3,5,49-trihydroxystilbene) and its natural precursor Polydatin (resveratrol-3-O-b-mono- D-glucoside, the glycoside form of resveratrol) combination, might have a cooperative antitumor effect on either growing or differentiated human adenocarcinoma colon cancer cells. While resveratrol cytotoxic action was due to its pro-oxidant properties. A number of studies have been focused on chemo-preventive use of resveratrol as antioxidant against cardiovascular diseases, aging and cancer. Human colon adenocarcinoma cells are resistant to chemotherapeutic agents, such as anthracyclines, that induce death by increasing the reactive oxygen species.