Polydatin, a natural precursor of resveratrol, induces cell cycle arrest and differentiation of human colorectal Caco-2 cell

Abstract

BackgroundHuman colon adenocarcinoma cells are resistant to chemotherapeutic agents, such as anthracyclines, that induce death by increasing the reactive oxygen species. A number of studies have been focused on chemo-preventive use of resveratrol as antioxidant against cardiovascular diseases, aging and cancer. While resveratrol cytotoxic action was due to its pro-oxidant properties. 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.MethodsThe 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. We have selected a synergistic combination and we have evaluated its effect on the biological and molecular mechanisms of cell death.ResultsSimultaneous exposure to polydatin and resveratrol produced synergistic antiproliferative effects compared with single compound treatment. We demonstrated that polydatin alone or in combination with resveratrol at 3:1 molar ratio synergistically modulated oxidative stress, cell cycle, differentiation and 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.ConclusionsFrom 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. Our data suggest the potential use of polydatin in combination chemotherapy for human colon cancer.

Targeting the ROS/PI3K/AKT/HIF‐1α/HK2 axis of breast cancer cells: Combined administration of Polydatin and 2‐Deoxy‐d‐glucose

“…26 The symbols * and ** denote significant differences of P < 0.05 and P < 0.01 versus the control group, respectively typical apoptotic proteins in cancer cells ( Figure 2H,I). 26 The symbols * and ** denote significant differences of P < 0.05 and P < 0.01 versus the control group, respectively typical apoptotic proteins in cancer cells ( Figure 2H,I).…”

“…PD is known to inhibit proliferation and induce apoptosis in breast cancer and colorectal cancer. 26,27 Therefore, we investigated disrupt the extracellular matrix (ECM) and then induce cancer cell migration and invasion. 28,29 In vitro, increased autocrine vascular endothelial growth factor (VEGF) is also considered to be one of the hallmarks of cancer invasion.…”

Some natural sources of substances with antitumor effects

“…Polidatin se smatra prirodnim prekurzorom rezveratrola koji deluje na kolorektalni kancer. 19,20 Ekstrakt korena vrste Astragalus memebranaceus decenijama je korišćen u tradicionalnoj Kineskoj medicini kao e kasni tretman prehlada, dijareja, stanja umora, anoreksije i srčanih oboljenja, ali je proučavan i kao potencijalno antitumorsko sredstvo. Ukupni saponini izolovani iz vrste Astragalus memebranaceus su pokazali inhibiciju rasta ćelijske linije kancera želuca, smanjujući invazivnost kancera i indukujući apoptozu.…”

Polydatin-induced cell apoptosis and cell cycle arrest are potentiated by Janus kinase 2 inhibition in leukemia cells

“…PD has been shown to have multiple beneficial therapeutic properties, including cardioprotective (7)(8)(9), hepatoprotective (10), neuroprotective (11) and anti-inflammatory (12) effects. PD has also been reported to have anti-cancer effects with activity against colon (13) and lung (14) cancer as well as nasopharyngeal carcinoma (15). However, to the best of our knowledge, the effects of PD on human leukemic cells have yet not been studied.…”