Polydatin, a Natural Precursor of Resveratrol, Induces Cell Cycle Arrest and Differentiation of Human Colorectal Caco-2 Cell

Overview

Journal J Transl Med

Publisher Biomed Central

Specialties Biomedical Engineering
General Medicine

Date 2013 Oct 22

PMID 24138806

Citations 38

Authors

Salvatore de Maria

Ilaria Scognamiglio

Angela Lombardi

Nicola Amodio

Michele Caraglia

Maria Carteni

Gianpietro Ravagnan

Paola Stiuso

Affiliations

Soon will be listed here.

Abstract

Background: Human 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.

Methods: 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. We have selected a synergistic combination and we have evaluated its effect on the biological and molecular mechanisms of cell death.

Results: Simultaneous 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.

Conclusions: From 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.

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References

Amodio N, Di Martino M, Foresta U, Leone E, Lionetti M, Leotta M . miR-29b sensitizes multiple myeloma cells to bortezomib-induced apoptosis through the activation of a feedback loop with the transcription factor Sp1. Cell Death Dis. 2012; 3:e436. PMC: 3542610. DOI: 10.1038/cddis.2012.175. View

Shaked H, Hofseth L, Chumanevich A, Chumanevich A, Wang J, Wang Y . Chronic epithelial NF-κB activation accelerates APC loss and intestinal tumor initiation through iNOS up-regulation. Proc Natl Acad Sci U S A. 2012; 109(35):14007-12. PMC: 3435160. DOI: 10.1073/pnas.1211509109. View

Amaravadi R, Thompson C . The survival kinases Akt and Pim as potential pharmacological targets. J Clin Invest. 2005; 115(10):2618-24. PMC: 1236693. DOI: 10.1172/JCI26273. View

Miki K, Kumar A, Yang R, Killeen M, Delude R . Extracellular activation of arginase-1 decreases enterocyte inducible nitric oxide synthase activity during systemic inflammation. Am J Physiol Gastrointest Liver Physiol. 2009; 297(4):G840-8. PMC: 2763806. DOI: 10.1152/ajpgi.90716.2008. View

Bamia C, Lagiou P, Buckland G, Grioni S, Agnoli C, Taylor A . Mediterranean diet and colorectal cancer risk: results from a European cohort. Eur J Epidemiol. 2013; 28(4):317-28. DOI: 10.1007/s10654-013-9795-x. View

Lanzilli G, Cottarelli A, Nicotera G, Guida S, Ravagnan G, Fuggetta M . Anti-inflammatory effect of resveratrol and polydatin by in vitro IL-17 modulation. Inflammation. 2011; 35(1):240-8. DOI: 10.1007/s10753-011-9310-z. View

Kovacic P, Somanathan R . Multifaceted approach to resveratrol bioactivity: Focus on antioxidant action, cell signaling and safety. Oxid Med Cell Longev. 2010; 3(2):86-100. PMC: 2952093. DOI: 10.4161/oxim.3.2.11147. View

Hoglen N, Bernstein H, Bernstein C, Payne C . Role of nitric oxide and peroxynitrite in bile salt-induced apoptosis: relevance to colon carcinogenesis. Nutr Cancer. 2000; 35(2):180-8. DOI: 10.1207/S15327914NC352_13. View

Koti R, Seifalian A, McBride A, Yang W, Davidson B . The relationship of hepatic tissue oxygenation with nitric oxide metabolism in ischemic preconditioning of the liver. FASEB J. 2002; 16(12):1654-6. DOI: 10.1096/fj.01-1034fje. View

10.

Fuggetta M, Lanzilli G, Tricarico M, Cottarelli A, Falchetti R, Ravagnan G . Effect of resveratrol on proliferation and telomerase activity of human colon cancer cells in vitro. J Exp Clin Cancer Res. 2006; 25(2):189-93. View

11.

Kumarapeli A, Wang X . Genetic modification of the heart: chaperones and the cytoskeleton. J Mol Cell Cardiol. 2004; 37(6):1097-109. DOI: 10.1016/j.yjmcc.2004.07.004. View

12.

Calderwood S, Khaleque M, Sawyer D, Ciocca D . Heat shock proteins in cancer: chaperones of tumorigenesis. Trends Biochem Sci. 2006; 31(3):164-72. DOI: 10.1016/j.tibs.2006.01.006. View

13.

Thom S, Bhopale V, Milovanova T, Yang M, Bogush M, Buerk D . Nitric-oxide synthase-2 linkage to focal adhesion kinase in neutrophils influences enzyme activity and β2 integrin function. J Biol Chem. 2013; 288(7):4810-8. PMC: 3576086. DOI: 10.1074/jbc.M112.426353. View

14.

Keklikoglu N, Koray M, Kocaelli H, Akinci S . iNOS expression in oral and gastrointestinal tract mucosa. Dig Dis Sci. 2007; 53(6):1437-42. DOI: 10.1007/s10620-007-0061-5. View

15.

Zhu C, Bassig B, Zaridze D, Boyle P, Dai M, Li Q . A birth cohort analysis of the incidence of ascending and descending colon cancer in the United States, 1973-2008. Cancer Causes Control. 2013; 24(6):1147-56. DOI: 10.1007/s10552-013-0193-1. View

16.

Herz F, Schermer A, HALWER M, Bogart L . Alkaline phosphatase in HT-29, a human colon cancer cell line: influence of sodium butyrate and hyperosmolality. Arch Biochem Biophys. 1981; 210(2):581-91. DOI: 10.1016/0003-9861(81)90224-1. View

17.

Ross G, Kang M, Akbarali H . Colonic inflammation alters Src kinase-dependent gating properties of single Ca2+ channels via tyrosine nitration. Am J Physiol Gastrointest Liver Physiol. 2010; 298(6):G976-84. PMC: 3061627. DOI: 10.1152/ajpgi.00056.2010. View

18.

Bradford M . A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 1976; 72:248-54. DOI: 10.1016/0003-2697(76)90527-3. View

19.

Wink D, Mitchell J . Chemical biology of nitric oxide: Insights into regulatory, cytotoxic, and cytoprotective mechanisms of nitric oxide. Free Radic Biol Med. 1998; 25(4-5):434-56. DOI: 10.1016/s0891-5849(98)00092-6. View

20.

Ronchetti D, Borghi V, Gaitan G, Herrero J, Impagnatiello F . NCX 2057, a novel NO-releasing derivative of ferulic acid, suppresses inflammatory and nociceptive responses in in vitro and in vivo models. Br J Pharmacol. 2009; 158(2):569-79. PMC: 2757697. DOI: 10.1111/j.1476-5381.2009.00324.x. View