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

Abstract

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...

Antiproliferative and toxicogenomic effects of resveratrol in bladder cancer cells with different TP53 status

“…Resveratrol is a polyphenolic compound found in grapes, berries, and peanuts . Regarding bladder cancer, it has already been demonstrated that resveratrol decreases cell viability, induces apoptosis, inhibits cell migration and induces cell cycle arrest in vitro (Stocco et al 2002;Lin et al 2012;Bai et al 2017). Furthermore, the antitumor potential of this natural product has been described in many tumor types (Ji et al 2015;Mohapatra et al 2015;Nie et al 2015;Selvaraj et al 2016).…”

“…Furthermore, the antitumor potential of this natural product has been described in many tumor types (Ji et al 2015;Mohapatra et al 2015;Nie et al 2015;Selvaraj et al 2016). Regarding bladder cancer, it has already been demonstrated that resveratrol decreases cell viability, induces apoptosis, inhibits cell migration and induces cell cycle arrest in vitro (Stocco et al 2002;Lin et al 2012;Bai et al 2017). Resveratrol is also able to reduce tumor growth in vivo (Bai et al 2009).…”

Therapeutic Effect of Resveratrol on Morphine-Induced Damage in Male Reproductive System of Mice by Reducing Nitric Oxide Serum Level

“…Resveratrol, found in many foods such as grape, is a phytoalexin with antioxidant, anti-inflammatory, and anti-cancer properties (Bai et al, 2017). The beneficial effects of resveratrol on male reproductive system have been approved by many authors addressing the antioxidant properties of this natural product.…”

Resveratrol suppresses colon cancer growth by targeting the AKT/STAT3 signaling pathway

“…It can also be extracted from the traditional Chinese plant Polygonum cuspidatum (5). Resveratrol has exhibited promising anticancer activity against breast cancer, ovarian cancer, leukemia, prostate cancer, liver cancer, melanoma, head and neck squamous cell carcinoma, thyroid cancer, and bladder cancer, via regulating cancer-related gene expression or cancer-associated signaling pathways (5)(6)(7)(8)(9)(10). The anticarcinogenic action of resveratrol is associated to its ability to neutralize reactive oxygen species (ROS) and to modulate cellular processes, such as apoptosis and cancer cell proliferation and differentiation (11).…”