Antiproliferative action in pancreatic cancer cells of a resveratrol derivative

The naturally occurring resveratrol (3,5,4′-trihydroxy-trans-stilbene) is a phytoalexin produced by plants in response to various stresses, promoting disease resistance. It received a great attention for its ability to impact on multiple key processes in cancer cell biology, although limitations in terms of poor solubility in water and extensive phase II metabolism reduce the bioavailability to less than 1%. Chemically, resveratrol contains a stibene scaffold that represents a suitable tool for chemical modifications with the aim to obtain derivatives with enhanced bioavailability and pharmacological activity. Bearing in mind that the 4′-OH was considered essential for the antioxidant/antitumor activity, we synthesized analogs of the resveratrol in which the 4′-OH was preserved, but the 3,5-OH moiety was replaced with 4-substituted phenyls. Some of the synthesized compounds have proven to be active in inhibiting cell viability across three distinct PC cell lines, as compared to the parent compound resveratrol. In this presentation, an insight into the more active compound will be described. In particular, we will refer to the ability of the most active analogue in modulating cancer-relevant molecular pathways, in a panel of PC cell lines with distinct genetic profiles. The results will provide to gain insights into the mechanisms involved in antiproliferative action, supporting the potential value in the search for effective and safe agents in PC treatment.