Resveratrol Promotes Self-digestion to Put Cancer to Sleep

Abstract

Resveratrol, a natural polyphenol present in a variety of food stuff, has been shown to exert preventive and curative anticancer activity in several in vitro and in vivo models. Such chemopreventive/anticancer activity has been linked to biochemical and epigenetic modifications of multiple pathways involved in carcinogenesis and metastasization. In this commentary, we focus on the recent work done in our laboratory showing that resveratrol has potential to prevent and cure cancer by promoting epigenetic-mediated autophagy-dependent tumor dormancy, an effect associated with re-education of the cancer-associated fibroblasts and reduced production of inflammatory cytokines in the tumor microenvironment. The clinical translation of the current knowledge on resveratrol anticancer activity is also discussed.

Keywords: Autophagy; Cytokines; Dormancy; Natural products; Tumor microenvironment.

Figure 1. The immunofluorescence co-staining for LC3/p21, BECLIN-1/DIRAS3, LC3/DIRAS3 and DIRAS3/STAT3 shows up-regulation of autophagy and autophagy-dependent dormancy in Pre-RV + RV and RV-treated mice (for treatment details see the text and reference [21]).

RV, resveratrol; LC3, light chain 3. Scale bar = 20 µm.

Figure 2. The cartoon illustrates the action of RV in the tumor microenvironment comprising fibroblasts and immune cells as well as the cancer cells which eventually leads to tumor dormancy.

ATG, autophagy; CCD, cancer cell dormancy; MTX, metastasis; RV, resveratrol; TME, tumor microenvironment; Fb, fibroblasts; Th, T CD4 lymphocyte; M, macrophages; CAF, cancer-associated fibroblasts; BM, basement membrane; IL, interleukin.