Abstract
3,3′,4,4′,5,5′-Hexahydroxy-trans-stilbene (M8) is a synthetic resveratrol derivative, advertised as a candidate drug highly effective against numerous malignancies. Because multiple tumors prone to M8 frequently metastasize into the peritoneal cavity, this study was aimed at establishing the effect of M8 on the growth and senescence of human peritoneal mesothelial cells (HPMCs), the largest cell population within the peritoneum, actively involved in the intraperitoneal spread of cancer. The study showed that M8, used at the highest non-toxic dose of 10 μM, impairs proliferation and accelerates senescence in cultured HPMCs via an oxidative stress-dependent mechanism. At the same time, soluble factors released to the environment by HPMCs that senesced prematurely in response to M8 promoted growth of colorectal and pancreatic carcinomas in vitro. These findings indicate that M8 may indirectly—through the modification of normal (mesothelial) cells phenotype—facilitate an expansion of cancer cells, which challenges the postulated value of this stilbene in chemotherapy.
Highlights
Resveratrol (3,4',5-trihydroxy-trans-stilbene; RVT) is a prototype stilbene widely acknowledged for its anti-ageing properties
In order to examine the effect of resveratrol analogue M8 on human peritoneal mesothelial cells (HPMCs) viability, confluent early-passage cells were exposed for 24 h to M8 in wide range of doses, and the MTT
We examined the effect of the synthetic resveratrol analogue M8 on viability and proliferation of normal human peritoneal mesothelial cells (HPMCs) in vitro
Summary
Resveratrol (3,4',5-trihydroxy-trans-stilbene; RVT) is a prototype stilbene widely acknowledged for its anti-ageing properties. It is believed that these effects of RVT are mainly related to an induction of NAD+-dependent histone deacetylases, sirtuins, which control such vital cellular processes as energy homeostasis, maintenance of genetic stability, and stress response [6] An another aspect of the RVT story which gained tons of attention over the past decade is its tumor-suppressing activity, associated with both anti-proliferative and pro-apoptotic effects exerted towards a wide range of malignancies [7,8]. In order to avoid these restrictions, numerous modified (hydroxylated or methylated) derivatives of RVT were synthesized, and their activity is being extensively investigated [9,10] These studies are based on a paradigm that an introduction of additional groups into the stilbene structure strengthens biological properties of RVT analogues [11]. Of these newly synthesized derivatives, high expectations are linked with
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