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

Gao, Qian; Yuan, Yuan; Gan, Huizhong; Peng, Qiong

doi:10.3892/ol.2015.2988

Cited by 78 publications

(56 citation statements)

References 52 publications

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“…Furthermore, it has previously been confirmed that resveratrol exerts antiproliferative and/or apoptotic effects on leukemia, prostate, breast and colon cancers cells in vitro (9)(10)(11)(12). Previous studies regarding the anticancer effects of resveratrol have focused on its anti-invasive and anti-metastatic activities (13)(14)(15). However, to the best of our knowledge, there is currently no evidence as to whether resveratrol may inhibit the migration and invasion of human bladder cancer cells.…”

Section: Introductionmentioning

confidence: 74%

Inhibitory effects of resveratrol on the adhesion, migration and invasion of human bladder cancer cells

Bai

Yang

Zhang

et al. 2016

Molecular Medicine Reports

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Abstract.Resveratrol is a polyphenolic compound, which has been revealed to induce apoptosis in numerous human cancer cells; however, the effects of resveratrol on the migration and invasion of human bladder cancer cells have not been reported. The present study aimed to evaluate the anti-metastatic potential of resveratrol against bladder cancer and its mechanism of action. The results indicated that resveratrol inhibits the adhesion, migration and invasion of bladder cancer cells in a dose-dependent manner. Resveratrol was shown to significantly inhibit the expression and secretion of matrix metalloproteinase (MMP)-2 and MMP-9 in bladder cancer cells. Furthermore, resveratrol suppressed the phosphorylation of c-Jun N-terminal kinase and extracellular signal-regulated protein kinase. In conclusion, the present study is the first, to the best of our knowledge, to demonstrate that resveratrol may be considered a novel anticancer agent for the treatment of bladder cancer via the inhibition of migration and invasion. IntroductionBladder cancer is the fourth most common type of cancer, and was the cause of >11,510 cases of cancer-associated mortality among men in the USA in 2014 (1). The majority of bladder cancer cases are noninvasive, low-grade transitional cell carcinoma (TCC); however, ≤30% of all diagnosed tumors are classified as invasive TCC, which is associated with high mortality (2). Notably, among all of the various types of cancer, bladder cancer exhibits a significantly high incidence of recurrence post-treatment, and therefore is recognized as the most expensive cancer to treat. Due to the high prevalence and frequent tumor recurrence associated with bladder cancer, the exploration of preventative strategies is required.Previous epidemiological and scientific studies have indicated that plant-derived phytochemicals may be beneficial in the prevention and treatment of cancer (3-5). Resveratrol is a polyphenolic compound, which is present in grapes (red wine), knotweed, peanuts, mulberries and other plants. Numerous studies have suggested that resveratrol may prevent the progression of various pathologies, including vascular diseases, ischemic injuries, cancer and neurodegenerative disorders (6-8). Furthermore, it has previously been confirmed that resveratrol exerts antiproliferative and/or apoptotic effects on leukemia, prostate, breast and colon cancers cells in vitro (9-12). Previous studies regarding the anticancer effects of resveratrol have focused on its anti-invasive and anti-metastatic activities (13-15). However, to the best of our knowledge, there is currently no evidence as to whether resveratrol may inhibit the migration and invasion of human bladder cancer cells.Metastasis is one of the hallmarks of advanced cancer progression, and cancer cell migration and invasion are crucial events in bladder cancer metastasis. Matrix metalloproteinases (MMPs), including MMP-2 and MMP-9, degrade the basement membrane and extracellular matrix (ECM), and are therefore considered crucial proteolytic protei...

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Section: Introductionmentioning

confidence: 74%

Inhibitory effects of resveratrol on the adhesion, migration and invasion of human bladder cancer cells

Bai

Yang

Zhang

et al. 2016

Molecular Medicine Reports

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“…In GC, tumorigenicity and EMT are regulated through activation of glioma-associated oncogene 1 (Gli1), a key member of the Hh signaling pathway [13–15]. Hh signaling during embryogenesis promotes tissue growth, tissue patterning, vascularization, and differentiation, all of which are processes that tumor cells employ in order to support tumor growth and facilitate metastasis [11].…”

Section: Introductionmentioning

confidence: 99%

Galectin-1 from cancer-associated fibroblasts induces epithelial–mesenchymal transition through β1 integrin-mediated upregulation of Gli1 in gastric cancer

Yan¹,

Tang²,

Xiong³

et al. 2016

J Exp Clin Cancer Res

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BackgroundGastric cancer (GC) is characterized by the excessive deposition of extracellular matrix, which is thought to contribute to this tumor’s malignant behavior. Epithelial-mesenchymal transition (EMT) is regarded as a crucial contributing factor to cancer progression. Galectin-1 (Gal-1), a β-galactoside-binding protein abundantly expressed in activated cancer-associated fibroblasts (CAFs), has been reported to be involved in GC progression and metastasis by binding to β1 integrin, which, in turn, can bind to matrix proteins and activate intracellular cascades that mediate EMT. Increasing evidence suggests that abnormal activation of the hedgehog (Hh) signaling pathway enhances GC cell migration and invasion. The purpose of our study is to explore the role of Gal-1 in the GC progression and metastasis as well as the regulatory mechanism.MethodsWe hypothesized that Gal-1 binding to β1 integrin would lead to paracrine signaling between CAFs and GC cells, mediating EMT by upregulating Gli1. Invasion and metastasis effects of the Gal-1 and Gli1 were evaluated using wound healing and invasion assay following transfection with mimics. Additionally, to facilitate the delineation of the role of the Hh signaling in GC, we monitored the expression level of associated proteins. We also evaluated the effects of β1 integrin on these processes. Furthermore, Gal-1 and Gli1 expression in GC patient samples were examined by immunohistochemistry and western blot to determine the correlation between their expression and clinicopathologic characteristics. The Kaplan-Meier method and Cox proportional hazards model were used to analyze the relationship of expression with clinical outcomes.ResultsGal-1 was found to induce EMT, GC cell migration and invasion. Further data showed that Gal-1 up-regulated Gli1 expression. β1 integrin was responsible for Gal-1-induced Gli1 expression and EMT. In clinical GC tissue, it confirmed a positive relationship between Gal-1 and Gli1 expression. Importantly, their high expression is correlated to poor prognosis.ConclusionGal-1 from CAFs binds to a carbohydrate structure in β1 integrin and plays an important role in the development of GC by inducing GC metastasis and EMT through targeting Gli1. This study highlights the potential therapeutic value of Gal-1 for suppression of GC metastasis.Electronic supplementary materialThe online version of this article (doi:10.1186/s13046-016-0449-1) contains supplementary material, which is available to authorized users.

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“…Gao and colleagues also demonstrated the anti-metastatic activity of resveratrol against gastric cancer cells by modulation of the Hedgehog signaling pathway through downregulation of Gli-1 expression. Moreover, resveratrol upregulated the expression of E-cadherin gene, decrease Snail protein and N-cadherin expression [234]. …”

Section: Metastasismentioning

confidence: 99%

Unraveling the Anticancer Effect of Curcumin and Resveratrol

et al. 2016

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Resveratrol and curcumin are natural products with important therapeutic properties useful to treat several human diseases, including cancer. In the last years, the number of studies describing the effect of both polyphenols against cancer has increased; however, the mechanism of action in all of those cases is not completely comprehended. The unspecific effect and the ability to interfere in assays by both polyphenols make this challenge even more difficult. Herein, we analyzed the anticancer activity of resveratrol and curcumin reported in the literature in the last 11 years, in order to unravel the molecular mechanism of action of both compounds. Molecular targets and cellular pathways will be described. Furthermore, we also discussed the ability of these natural products act as chemopreventive and its use in association with other anticancer drugs.

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

Cited by 78 publications

References 52 publications

Inhibitory effects of resveratrol on the adhesion, migration and invasion of human bladder cancer cells

Inhibitory effects of resveratrol on the adhesion, migration and invasion of human bladder cancer cells

Galectin-1 from cancer-associated fibroblasts induces epithelial–mesenchymal transition through β1 integrin-mediated upregulation of Gli1 in gastric cancer

Unraveling the Anticancer Effect of Curcumin and Resveratrol

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