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Int. J. Mol. Sci. 2013, 14(11), 22483-22498; doi:10.3390/ijms141122483

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

1
Laboratory of Gerontology, Department of Pathophysiology, Poznań University of Medical Sciences, Święcickiego 6 Str., Poznań 60-781, Poland
2
Department of Chemical Technology of Drugs, Poznań University of Medical Sciences, Grunwaldzka 6, Poznań 60-780, Poland
3
Laboratory of Cytometry, Nencki Institute of Experimental Biology, Polish Academy of Sciences, Pasteura 3, Warsaw 02-093, Poland
These authors contributed equally to this work.
*
Author to whom correspondence should be addressed.
Received: 26 August 2013 / Revised: 18 October 2013 / Accepted: 1 November 2013 / Published: 14 November 2013
(This article belongs to the Collection Programmed Cell Death and Apoptosis)
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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. View Full-Text
Keywords: cancer metastases; mesothelial cells; peritoneal cavity; replicative senescence; stilbenes cancer metastases; mesothelial cells; peritoneal cavity; replicative senescence; stilbenes
This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).

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Mikuła-Pietrasik, J.; Sosińska, P.; Wierzchowski, M.; Piwocka, K.; Książek, K. 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. Int. J. Mol. Sci. 2013, 14, 22483-22498.

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