Resveratrol Inhibits the Migration and Metastasis of MDA-MB-231 Human Breast Cancer by Reversing TGF-β1-Induced Epithelial-Mesenchymal Transition

Abstract

Metastasis is a major cause of death in patients with breast cancer. In the process of cancer development, epithelial-mesenchymal transition (EMT) is crucial to promoting the invasion and migration of tumor cells. In a previous study, the role of resveratrol in migration and metastasis was investigated in MDA-MB-231 (MDA231) human breast cancer cells and a xenograft-bearing mouse model. Additionally, the related mechanism was explored. In the present study, in vitro Transwell assays showed that resveratrol can inhibit the migration of transforming growth factor (TGF)-β1-induced MDA231 cells in a concentration-dependent manner. An enzyme-linked immunosorbent assay (ELISA) showed that resveratrol can reduce the secretion of matrix metalloproteinase (MMP)-2 and MMP-9. Immunofluorescence was performed to confirm the expression of EMT-related markers. Immunofluorescence assays confirmed that resveratrol changed the expression of the EMT-related markers E-cadherin and vimentin. Western blot analysis demonstrated that resveratrol decreased the expression levels of MMP-2, MMP-9, Fibronectin, α-SMA, P-PI3K, P-AKT, Smad2, Smad3, P-Smad2, P-Smad3, vimentin, Snail1, and Slug, as well as increased the expression levels of E-cadherin in MDA231 cells. In vivo, resveratrol inhibited lung metastasis in a mouse model bearing MDA231 human breast cancer xenografts without marked changes in body weight or liver and kidney function. These results indicate that resveratrol inhibits the migration of MDA231 cells by reversing TGF-β1-induced EMT and inhibits the lung metastasis of MDA231 human breast cancer in a xenograft-bearing mouse model.

Potential Adverse Effects of Resveratrol: A Literature Review

“…By acting as a cytotoxic agent, RE can halt the progression and metastasis of cancer cells through the inhibition of angiogenesis and invasion of primary tumor cells. Hence, RE can be used to prevent cancer formation at its early stages or halt the progression and subsequent metastasis by acting as a cytotoxic agent [202][203][204][205][206].…”

Modulation of non-coding RNAs by resveratrol in ovarian cancer cells: In silico analysis and literature review of the anti-cancer pathways involved

“…RV is a nutraceutical polyphenol with anti-cancer potential. 22 , 37 , 38 RV has been shown effective in causing cancer cell death and cancer cell senescence 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 and to inhibit cancer cell invasion and metastasis 30 , 47 , 48 , 49 in several in vitro and in vivo models, including ovarian cancer. 30 , 42 , 49 It has been shown that autophagy contributes to RV-induced apoptosis in ovarian cancer cells.…”

Resveratrol Modulates Transforming Growth Factor-Beta (TGF-β) Signaling Pathway for Disease Therapy: A New Insight into Its Pharmacological Activities

“…In breast cancer, TGF-β can stimulate EMT via Smad2 and Smad3 activation, leading to an increase in N-cadherin and vimentin levels, and a decrease in E-cadherin levels. The administration of Res suppresses the metastasis of breast cancer (under both in vitro and in vivo conditions) via the inhibition of TGF-β1 and down-regulation of Smad2 and Smad3 [ 177 ]. TGF-β also contributes to the migration and malignant behavior of lung cancer.…”