Journal Article

Resveratrol Regulates Colorectal Cancer Cell Invasion by Modulation of Focal Adhesion Molecules

Shakibaei, Mehdi, Buhrmann, Constanze, Goel, Ajay, Shayan, Parviz

2017

Overview

Resveratrol, a safe and multi-targeted agent, has been associated with suppression of survival, proliferation and metastasis of cancer, however, the underlying mechanisms for its anti-cancer activity, particularly on cellular signaling during cancer cell migration still remain poorly understood. We investigated the invasion response of two human colorectal cancer (CRC) cells (HCT116 and SW480) to resveratrol and studied the effect of specific pharmacological inhibitors, cytochalasin D (CytD) and focal adhesion kinase-inhibitor (FAK-I) on FAK, cell viability and migration in CRC. We found that resveratrol altered cell phenotype of both CRC cells, reduced cell viability and the results were comparable to FAK-I and CytD. These effects of resveratrol were associated with marked Sirt1 up-regulation, FAK down-regulation, inhibition of focal adhesion and potentiation of effects by combinatorial treatment of resveratrol and inhibitors. Interestingly, inhibition of FAK with FAK-I or treatment with CytD suppressed resveratrol-induced Sirt1 up-regulation and markedly down-regulated FAK expression. Resveratrol or combination treatment with inhibitors significantly activated caspase-3 and potentiated apoptosis. Moreover, resveratrol suppressed invasion and colony forming capacity, cell proliferation, β1-Integrin expression and activation of FAK of cells in alginate tumor microenvironment, similar to FAK-I or CytD. Finally, we demonstrated that resveratrol, FAK-I or CytD inhibited activation of NF-κB, suppressed NF-κB-dependent gene end-products involved in invasion, metastasis, and apoptosis; and these effects of resveratrol were potentiated by combination treatment with FAK-I or CytD. Our data illustrated that the anti-invasion effect of resveratrol by inhibition of FAK activity has a potential beneficial role in disease prevention and therapeutic management of CRC.

• Publisher: MDPI AG,MDPI
• Subject: alginates / antineoplastic activity / Antineoplastic Agents - pharmacology / Apoptosis / Apoptosis - drug effects / Caspase 3 - metabolism / caspase-3 / CD29 antigen / Cell adhesion & migration / Cell Adhesion Molecules - metabolism / cell communication / cell movement / Cell Movement - drug effects / cell proliferation / cell viability / Colorectal cancer / colorectal neoplasms / Colorectal Neoplasms - drug therapy / Colorectal Neoplasms - metabolism / Colorectal Neoplasms - pathology / cytochalasin D / disease prevention / Dose-Response Relationship, Drug / enzyme inhibitors / Focal Adhesion Kinase 1 - antagonists & inhibitors / Focal Adhesion Kinase 1 - metabolism / focal adhesions / Focal Adhesions - drug effects / Focal Adhesions - metabolism / Focal Adhesions - pathology / genes / HCT116 Cells / human cell lines / Humans / Integrin beta1 - metabolism / Kinases / Metastasis / neoplasm cells / Neoplasm Invasiveness / NF-kappa B - metabolism / non-specific protein-tyrosine kinase / Protein Kinase Inhibitors - pharmacology / Resveratrol / Signal Transduction - drug effects / Sirtuin 1 - metabolism / Stilbenes - pharmacology / therapeutics / Time Factors / transcription factor NF-kappa B / Tumor Microenvironment