Resveratrol inhibits the hedgehog signaling pathway and epithelial-mesenchymal transition and suppresses gastric cancer invasion and metastasis

Oncology Letters

Volumn 9, Issue 5, 2015, Pages 2381-2387

  Gao, Qian ^a   Yuan, Yuan ^a   Gan, Hui‑Zhong ^a   Peng, Qiong ^a  

^a ANHUI MEDICAL UNIVERSITY   (China)

Author keywords

Cyclopamine; Gastric cancer epithelial mesenchymal transition; Hedgehog signaling pathway; Resveratrol

Indexed keywords

CYCLOPAMINE; DIMETHYL SULFOXIDE; MESSENGER RNA; NERVE CELL ADHESION MOLECULE; RESVERATROL; SONIC HEDGEHOG PROTEIN; TRANSCRIPTION FACTOR GLI1; TRANSCRIPTION FACTOR SNAIL; UVOMORULIN;

ARTICLE; CELL PROLIFERATION ASSAY; CELL VIABILITY; CONTROLLED STUDY; EPITHELIAL MESENCHYMAL TRANSITION; HUMAN; HUMAN CELL; IC50; IN VITRO STUDY; INTRACELLULAR SIGNALING; METASTASIS; MTT ASSAY; PROTEIN EXPRESSION; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION; RNA ISOLATION; STOMACH CANCER; TUMOR INVASION; WESTERN BLOTTING;

EID: 84925437198     PISSN: 17921074     EISSN: 17921082     Source Type: Journal    
DOI: 10.3892/ol.2015.2988     Document Type: Article

References (55)

1. Parkin DM: Global cancer statistics in the year 2000. Lancet Oncol 2: 533‑543, 2001.
2. Khosravi Shahi P, Díaz Muñoz de la Espada VM García Alfonso P, et al: Management of gastric adenocarcinoma Clin Transl Oncol 9: 438‑442, 2007.
3. Radisky DC: Epithelial‑mesenchymal transition. J Cell Sci 118: 4325‑4326, 2005.
4. Thiery JP and Sleeman JP: Complex networks orchestrate epithelial‑mesenchymal transitions. Nat Rev Mol Cell Biol 7: 131‑142, 2006.
5. Chang CJ, Chao CH, Xia W, et al: p53 regulates epithelial‑mesenchymal transition and stem cell properties through modulating miRNAs. Nat Cell Biol 13: 317‑323, 2011.
6. Thier y JP, Acloque H, Huang RY and Nieto MA: Epithelial‑mesenchymal transitions in development and disease. Cell 139: 871‑890, 2009.
7. Voulgari A and Pintzas A: Epithelial‑mesenchymal transition in cancer metastasis: mechanisms markers and strategies to overcome drug resistance in the clinic. Biochim Biophys Acta 1796: 75‑90, 2009.
8. Kundu JK and Surh YJ: Cancer chemopreventive and therapeutic potential of resveratrol: mechanistic perspectives. Cancer Lett 269: 243‑261, 2008.
9. Xie D, Gore C, Liu J, et al: Role of DAB2IP in modulating epithelial‑to‑mesenchymal transition and prostate cancer metastasis. Proc Natl Acad Sci USA 107: 2485‑2490, 2010.
10. Gjerdrum C, Tiron C, Høiby T, et al: Axl is an essential epithelial‑to‑mesenchymal transition‑induced regulator of breast cancer metastasis and patient survival. Proc Natl Acad Sci USA 107: 1124‑1129, 2010.
11. Moreno-Bueno G, Peinado H, Molina P, et al: The morphological and molecular features of the epithelial‑to‑mesenchymal transition. Nat Protoc 4: 1591‑1613, 2009.
12. Li X, Deng W, Nail CD, Bailey SK, Kraus MH, Ruppert JM and Lobo‑Ruppert SM: Snail induction is an early response to Gli1 that determines the efficiency of epithelial transformation. Oncogene 25: 609‑621, 2006.
13. Louro ID, Bailey EC, Li X, et al: Comparative gene expression profile analysis of GLI and c‑MYC in an epithelial model of malignant transformation. Cancer Res 62: 5867‑5873, 2002.
14. McMahon AP, Ingham PW and Tabin CJ: Developmental roles and clinical significance of hedgehog signaling. Curr Top Dev Biol 53: 1‑114, 2003.
15. Lee J, Platt KA, Censullo P and Ruiz i Altaba A: Gli1 is a target of Sonic hedgehog that induces ventral neural tube development. Development 124: 2537‑2552, 1997.
16. Ohta M, Tateishi KKanai Fet al, p53‑independent negative regulation of p21/cyclin‑dependent kinase‑interacting protein 1 by the sonic hedgehog‑glioma‑associated oncogene 1 pathway in gastric carcinoma cells. Cancer Res 65: 10822‑10829, 2005.
17. Watkins DN, Berman DM, Burkholder SG, Wang B, Beachy PA and Baylin SB: Hedgehog signalling within airway epithelial progenitors and in small‑cell lung cancer. Nature 422: 313‑317, 2003.
18. Kubo M, Nakamura M, Tasaki A, et al: Hedgehog signaling pathway is a new therapeutic target for patients with breast cancer. Cancer Res 64: 6071‑6074 2004.
19. Mimeault M, Moore E, Moniaux N, et al: Cytotoxic effects induced by a combination of cyclopamine and gefitinib, the selective hedgehog and epidermal growth factor receptor signaling inhibitors, in prostate cancer cells. Int J Cancer 118: 1022‑1031, 2006.
20. Qualtrough D, Buda A, Gaffield W, Williams AC and Paraskeva C: Hedgehog signalling in colorectal tumour cells: induction of apoptosis with cyclopamine treatment. Int J Cancer 110: 831‑837, 2004.
21. Thayer SP, di Magliano MP, Heiser PW, et al: Hedgehog is an early and late mediator of pancreatic cancer tumorigenesis. Nature 425: 851‑856, 2003.
22. Yoo YA, Kang MH, Lee HJ, et al: Sonic hedgehog pathway promotes metastasis and lymphangiogenesis via activation of Akt, EMT and MMP‑9 pathway in gastric cancer. Cancer Res 71: 7061‑7070, 2011.
23. Yanai K, Nagai S, Wada J, et al: Hedgehog signaling pathway is a possible therapeutic target for gastric cancer. J Surg Oncol 95: 55‑62, 2007.
24. Wang Y, Catana F, Yang Y, Roderick R and van Breemen RB: An LC‑MS method for analyzing total resveratrol in grape juice, cranberry juice and in wine. J Agric Food Chem 50: 431‑435, 2002.
25. Burns J, Yokota T, Ashihara H, Lean ME and Crozier A: Plant foods and herbal sources of resveratrol. J Agric Food Chem 50: 3337‑3340, 2002.
26. Qadri SM, Föller M and Lang F: Inhibition of suicidal erythrocyte death by resveratrol. Life Sci 85: 33‑38, 2009.
27. Baur JA and Sinclair DA: Therapeutic potential of resveratrol: the in vivo evidence. Nat Rev Drug Discov 5: 493‑506, 2006.
28. Kundu JK and Surh YJ: Cancer chemopreventive and therapeutic potential of resveratrol: mechanistic perspectives. Cancer Lett 269: 243‑261, 2008.
29. Wang H, Zhang H, Tang L, et al: Resveratrol inhibits TGF‑β1‑induced epithelial‑to‑mesenchymal transition and suppresses lung cancer invasion and metastasis. Toxicology303: 139‑146, 2013.
30. Li W, Ma J, Ma Q, et al: Resveratrol inhibits the epithelial‑mesenchymal transition of pancreatic cancer cells via suppression of the PI‑3 K/Akt/NF‑κB pathway. Curr Med Chem 20: 4185‑4194, 2013.
31. Vergara D, Valente CM, Tinelli A, et al: Resveratrol inhibits the epidermal growth factor‑induced epithelial mesenchymal transition in MCF‑7 cells. Cancer Lett 310: 1‑8, 2011.
32. Slusarz A, Shenouda NS, Sakla MS, et al: Common botanical compounds inhibit the hedgehog signaling pathway in prostate cancer. Cancer Res 70: 3382‑3390, 2010.
33. Sarkar FH, Li Y, Wang Z and Kong D: The role of nutraceuticals in the regulation of Wnt and Hedgehog signaling in cancer. Cancer Metastasis Rev 29: 383‑394, 2010.
34. Shakibaei M, Harikumar KB and Aggarwal BB: Resveratrol addiction: to die or not to die. Mol Nutr Food Res 53: 115‑128, 2009.
35. Bisht K, Wagner KH and Bulmer AC: Curcumin, resveratrol and flavonoids as anti‑inflammatory, cyto‑ and DNA‑protective dietary compounds. Toxicology 278: 88‑100, 2010.
36. Michels G, Wätjen W, Weber N, et al: Resveratrol induces apoptotic cell death in rat H4IIE hepatoma cells but necrosis in C6 glioma cells. Toxicology 225: 173‑182, 2006.
37. Busquets S, Ametller E, Fuster G, et al: Resveratrol a natural diphenol, reduces metastatic growth in an experimental cancer model. Cancer Lett 245: 144‑148, 2007.
38. Olas B, Wachowicz B, Tomczak A, et al: Comparative anti‑platelet and antioxidant properties of polyphenol‑rich extracts from: berries of Aronia melanocarpa, seeds of grape and bark of Yucca schidigera in vitro. Platelets 19: 70‑77, 2008.
39. Knobloch J, Hag H, Jungck D, Urban K and Koch A: Resveratrol impairs the release of steroid‑resistant cytokines from bacterial endotoxin‑exposed alveolar macrophages in chronic obstructive pulmonary disease. Basic Clin Pharmacol Toxicol 109: 138‑143, 2011.
40. Lee SY, Lee HJ, Sikder MA, et al: Resveratrol inhibits mucin gene expression production and secretion from airway epithelial cells. Phytother Res 26: 1082‑1087, 2012.
41. Nüsslein-Volhard C and Wieschaus E: Mutations affecting segment number and polarity in Drosophila. Nature 287: 795‑801, 1980.
42. Chang DT, López A, von Kessler DP, et al: Products, genetic linkage and limb patterning activity of a murine hedgehog gene. Development 120: 3339‑3353, 1994.
43. Echelard Y, Epstein DJSt‑JacquesB, et al, : Sonic hedgehog, a member of a family of putative signaling molecules, is implicated in the regulation of CNS polarity. Cell 75: 1417‑1430, 1993.
44. Krauss S, Concordet JP and Ingham PW: A functionally conserved homolog of the Drosophila segment polarity gene hh is expressed in tissues with polarizing activity in zebrafish embryos. Cell 75: 1431‑1444, 1993.
45. Riddle RD, Johnson RL, Laufer E and Tabin C: Sonic hedgehog mediates the polarizing activity of the ZPA. Cell 75: 1401‑1416, 1993.
46. Lum L and Beachy PA: The hedgehog response network: sensors, switches and routers. Science 304: 1755‑1759, 2004.
47. Eaton S: Multiple roles for lipids in the Hedgehog signalling pathway. Nat Rev Mol Cell Biol 9: 437‑445, 2008.
48. Pasca di Magliano M and Hebrok M: Hedgehog signalling in cancer formation and maintenance. Nat Rev Cancer 3: 903‑911, 2003.
49. Ingham PW and McMahon AP: Hedgehog signaling in animal development: paradigms and principles. Genes Dev 15: 3059‑3087, 2001.
50. Louro ID, Bailey EC, Li X, et al: Comparative gene expression profile analysis of GLI1 and c‑MYC in an epithelial model of malignant transformation. Cancer Res 62: 5867‑5873, 2002.
51. Shankar S, Nall D, Tang SN, Meeker D, Passarini J, Sharma J and Srivastava RK: Resveratrol inhibits pancreatic cancer stem cell characteristics in human and KrasG12D transgenic mice by inhibiting pluripotency maintaining factors and epithelial‑mesenchymal transition. PLoS One 6: e16530, 2011.
52. Incardona JP, Gaffield W, Kapur RP and Roelink H: The teratogenic Veratrum alkaloid cyclopamine inhibits Sonic hedgehog signal transduction. Development 125: 3553‑3562, 1998.
53. Wang Y, Zhou Z, Walsh CT and McMahon AP: Selective translocation of intracellular Smoothened to the primary cilium in response to Hedgehog pathway modulation. Proc Natl Acad Sci USA 106: 2623‑2628, 2009.
54. Chen JK, Taipale J, Cooper MK and Beachy PA: Inhibition of Hedgehog signaling by direct binding of cyclopamine to Smoothened. Genes Dev 16: 2743‑2748, 2002.
55. Scales SJ and de Sauvage FJ: Mechanisms of Hedgehog pathway activation in cancer and implications for therapy. Trends Pharmacol Sci 30: 303‑312, 2009.