Synthetic resveratrol analogue, 3,3',4,4',5,5'-hexahydroxy-trans-stilbene, accelerates senescence in peritoneal mesothelium and promotes senescence-dependent growth of gastrointestinal cancers.
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.
Laboratory of Gerontology, Department of Pathophysiology, Poznań University of Medical Sciences, Święcickiego 6 Str., Poznań 60-781, Poland. kksiazek@ump.edu.pl.
Justyna
J
Mikuła-Pietrasik
Patrycja
P
Sosińska
Marcin
M
Wierzchowski
Katarzyna
K
Piwocka
Krzysztof
K
Książek
D063646:Carcinogenesis / Q000187:drug effects; D045744:Cell Line, Tumor; D016922:Cellular Senescence / Q000187:drug effects*; D004848:Epithelium / Q000187:drug effects / Q000254:growth & development; D005770:Gastrointestinal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D018384:Oxidative Stress; D010534:Peritoneal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D010537:Peritoneum / Q000378:metabolism / Q000473:pathology; D011748:Pyrogallol / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D000077185:Resveratrol; D013267:Stilbenes / Q000009:adverse effects / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
C514772:3,3',4,4',5,5'-hexahydroxystilbene; D013267:Stilbenes; D011748:Pyrogallol; D000077185:Resveratrol