"Resveratrol Contrast Cancer Cell Invasion through Induction of Autophagy: Mechanisms and Pathways"
Ciro Isidoro, M.D., Ph.D.
Department of General Pathology
Università del Piemonte Orientale
Resveratrol is a naturally occurring polyphenol with the potential to inhibit cancer cell migration. Here we show that Resveratrol counteracts the cell migration and invasion stimulatory effects of IL-6 (a cytokine released by cancer associated fibroblasts) and of Lysophosphatidic acid (LPA, a small phospholipid released by cancer cells), both known to promote ovarian cancer metastasis. Transcriptomic and microRNomic analyses showed that Resveratrol and IL-6 regulated in an opposite manner the expression of RNA messengers and of microRNAs involved in cell locomotion and extracellular matrix remodeling associated with the invasive properties of ovarian cancer cells. Further, Resveratrol and LPA regulated in an opposite manner the expression of Bmi-1, a polycomb protein of the HedgeHog pathway involved in cancer cell stemness and metastasis. We show that the pathways triggered by Resveratrol converge in the activation of autophagy in cancer cells and that this process is sufficient to inhibit cancer cell migration and invasion.