Influence of Polydatin on the Tumor Microenvironment In Vitro: Studies with a Colon Cancer Cell Model

Abstract

The tumor microenvironment of colon carcinoma, the site at which tumor cells and the host immune system interact, is influenced by signals from tumor cells, immunocompetent cells, and bacterial components, including LPS. A large amount of LPS is available in the colon, and this could promote inflammation and metastasis by enhancing tumor cell adhesion to the endothelium. Polydatin (PD), the 3-β-D-glucoside of trans-resveratrol, is a polyphenol with anti-cancer, anti-inflammatory, and immunoregulatory effects. This study was designed to explore whether PD is able to produce antiproliferative effects on three colon cancer lines, to reduce the expression of adhesion molecules that are upregulated by LPS on endothelial cells, and to decrease the proinflammatory cytokines released in culture supernatants. Actually, we investigated the effects of PD on tumor growth in a coculture model with human mononuclear cells (MNCs) that mimics, at least in part, an in vitro tumor microenvironment. The results showed that PD alone or in combination with MNC exerts antiproliferative and proapoptotic effects on cancer cells, inhibits the production of the immunosuppressive cytokine IL-10 and of the proinflammatory cytokines upregulated by LPS, and reduces E-selectin and VCAM-1 on endothelial cells. These data provide preclinical support to the hypothesis that PD could be of potential benefit as a therapeutic adjuvant in colon cancer treatment and prevention.

Aerobic Exercise-Mimetic Effects of Resveratrol on the Prevention of Vascular Endothelial Senescence

“…Specifically, we found that resveratrol treatment led to a decrease in the proportion of senescence-associated β-galactosidase positive cells, a well-established marker of cellular senescence. This finding is consistent with previous studies that have demonstrated the anti-aging effects of resveratrol on the cardiovascular system, including its ability to improve endothelial function and reduce oxidative stress and inflammation [26,27].…”

Role of natural products in tumor therapy from basic research and clinical perspectives

“…For example, resveratrol derivatives (CS and DMU-281) exert a marked anti-cancer activity on CRC cells, effectively inducing apoptosis and cell cycle arrest [18,19]. Similarly, the 3-β-D-glucoside of trans-resveratrol exerts anti-proliferative and pro-apoptotic effects on CRC cells by regulating modulation of the tumor microenvironment [20]. Additionally, Lin et al [21] reported that oxyresveratrol inhibits CRC cell migration by regulating EMT and microRNA (miRNAs).…”