Molecular Mechanisms of Resveratrol Action in Lung Cancer Cells Using Dual Protein and Microarray Analyses

Abstract

Resveratrol, a natural phytoestrogen found in red wine and a variety of plants, is reported to have protective effects against lung cancer; however, there is little work directed toward the understanding of the mechanism of its action in this disease. In this study, we used a combination of experimental approaches to understand the biological activity and molecular mechanisms of resveratrol. Microarray gene expression profiling and high-throughput immunoblotting (PowerBlot) methodologies were employed to gain insights into the molecular mechanisms of resveratrol action in human lung cancer cells. In this report, we confirm the up-regulation of p53 and p21 and the induction of apoptosis by the activation of the caspases and the disruption of the mitochondrial membrane complex. We show the arrest of A549 cells in the G 1 phase of cell cycle in the presence of resveratrol and also report alterations in both gene and protein expressions of cyclin A, chk1, CDC27, and Eg5. Furthermore, the results indicated that resveratrol action is mediated via the transforming growth factor-B pathway, particularly through the Smad proteins. Results showed the down-regulation of the Smad activators 2 and 4 and the up-regulation of the repressor Smad 7 as a result of resveratrol treatment. Resveratrol is a potent inhibitor of A549 lung cancer cell growth, and our results suggest that resveratrol may be a promising chemopreventive or chemotherapeutic agent for lung cancer.

Up-Regulation of Human Prostaglandin Reductase 1 Improves the Efficacy of Hydroxymethylacylfulvene, an Antitumor Chemotherapeutic Agent

“…Furthermore, microarray studies regarding cellular responses to D3T or resveratrol have failed to implicate alterations in membrane transport (Kwak et al, 2003;Whyte et al, 2007). Despite these data, transport and repair have not been explicitly evaluated in this study and cannot be excluded as possible factors contributing to cytotoxicity.…”

Resveratrol Protects Human Endothelium from H2O2-Induced Oxidative Stress and Senescence via SirT1 Activation

“…It possesses the ability to scavenge oxidatively generated free radicals, and prevents tumor progression by blocking NF-B expression, leading to cancer cell apoptosis 16,[23][24][25][26][27] . RV also has promising neuroprotective and cardioprotective effects, as well as slowing aging and delaying the onset of chronic diseases 23,[28][29][30] .…”

Red wine consumption and risk of prostate cancer: The California Men's Health Study

“…1,2 Resveratrol inhibits cancer cell growth in many cell lines, including cancers of the lung, prostate, colon, breast and ovaries. [3][4][5][6][7][8][9][10][11][12][13][14] Resveratrol also reduces tumor incidence in animal models by interfering with carcinogenesis through a wide array of anti-cancer actions. Several animal studies have demonstrated the ability of resveratrol to inhibit prostate cancer development by downregulating androgen receptors, inducing apoptosis/cell cycle arrest and inhibiting disease progression.…”