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Article: 2,3′,4,4′,5′-Pentamethoxy-trans-stilbene, a resveratrol derivative, inhibits colitis-associated colorectal carcinogenesis in mice

Title2,3′,4,4′,5′-Pentamethoxy-trans-stilbene, a resveratrol derivative, inhibits colitis-associated colorectal carcinogenesis in mice
Authors
KeywordsChemoprevention
Colitis
Colon Carcinogenesis
Resveratrol Derivatives
Issue Date2010
PublisherJohn Wiley & Sons Ltd. The Journal's web site is located at http://www.wiley.com/bw/journal.asp?ref=0007-1188&site=1
Citation
British Journal Of Pharmacology, 2010, v. 160 n. 6, p. 1352-1361 How to Cite?
AbstractBackground and purpose: Resveratrol, a naturally occurring polyphenolic antioxidant, has been shown to exhibit chemoprophylactic effects on cancer development. Previously, we reported that 2,3′,4,4′,5′- pentamethoxy-trans-stilbene (PMS), a methoxylated resveratrol derivative, exerted a highly potent anti-proliferative effect on human colon cancer cells as compared with its parent compound. In the present study, the chemopreventive effect of PMS was evaluated in a mouse model of colitis-associated colon carcinogenesis. Experimental approach: Seven-week-old Balb/c mice were injected i.p. with 10 mg·kg -1 azoxymethane (AOM). After 1 week, 3% dextran sodium sulphate (DSS) was administered in the drinking water for 7 days followed by 14 days of tap water for recovery, and this cycle was repeated twice. Key results: Intragastric administration of PMS (25, 50 mg·kg -1 body weight) for 16 weeks significantly reduced the multiplicity of colonic neoplasms by 15% and 35% (P < 0.01) respectively. Moreover, PMS at 50 mg·kg -1 inhibited colon cancer cell proliferation and promoted apoptosis. Such changes were accompanied by reduction of Akt (protein kinase B) phosphorylation, inactivation of β-catenin and down-regulation of inducible nitric oxide synthase. In parallel, in vitro studies also demonstrated that PMS inhibited proliferation and induced apoptosis in the murine colon adenocarcinoma cell line Colon26 with concomitant inhibition of Akt phosphorylation and inactivation of β-catenin. Conclusions and implications: PMS effectively suppressed colon carcinogenesis in an AOM/DSS animal model and may merit further clinical investigation as a chemoprophylactic agent against colitis-associated colon cancer in humans. © 2010 The British Pharmacological Society.
Persistent Identifierhttp://hdl.handle.net/10722/179197
ISSN
2015 Impact Factor: 5.259
2015 SCImago Journal Rankings: 2.368
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorLi, Hen_US
dc.contributor.authorWu, WKKen_US
dc.contributor.authorLi, ZJen_US
dc.contributor.authorChan, KMen_US
dc.contributor.authorWong, CCMen_US
dc.contributor.authorYe, CGen_US
dc.contributor.authorYu, Len_US
dc.contributor.authorSung, JJYen_US
dc.contributor.authorCho, CHen_US
dc.contributor.authorWang, Men_US
dc.date.accessioned2012-12-19T09:52:47Z-
dc.date.available2012-12-19T09:52:47Z-
dc.date.issued2010en_US
dc.identifier.citationBritish Journal Of Pharmacology, 2010, v. 160 n. 6, p. 1352-1361en_US
dc.identifier.issn0007-1188en_US
dc.identifier.urihttp://hdl.handle.net/10722/179197-
dc.description.abstractBackground and purpose: Resveratrol, a naturally occurring polyphenolic antioxidant, has been shown to exhibit chemoprophylactic effects on cancer development. Previously, we reported that 2,3′,4,4′,5′- pentamethoxy-trans-stilbene (PMS), a methoxylated resveratrol derivative, exerted a highly potent anti-proliferative effect on human colon cancer cells as compared with its parent compound. In the present study, the chemopreventive effect of PMS was evaluated in a mouse model of colitis-associated colon carcinogenesis. Experimental approach: Seven-week-old Balb/c mice were injected i.p. with 10 mg·kg -1 azoxymethane (AOM). After 1 week, 3% dextran sodium sulphate (DSS) was administered in the drinking water for 7 days followed by 14 days of tap water for recovery, and this cycle was repeated twice. Key results: Intragastric administration of PMS (25, 50 mg·kg -1 body weight) for 16 weeks significantly reduced the multiplicity of colonic neoplasms by 15% and 35% (P < 0.01) respectively. Moreover, PMS at 50 mg·kg -1 inhibited colon cancer cell proliferation and promoted apoptosis. Such changes were accompanied by reduction of Akt (protein kinase B) phosphorylation, inactivation of β-catenin and down-regulation of inducible nitric oxide synthase. In parallel, in vitro studies also demonstrated that PMS inhibited proliferation and induced apoptosis in the murine colon adenocarcinoma cell line Colon26 with concomitant inhibition of Akt phosphorylation and inactivation of β-catenin. Conclusions and implications: PMS effectively suppressed colon carcinogenesis in an AOM/DSS animal model and may merit further clinical investigation as a chemoprophylactic agent against colitis-associated colon cancer in humans. © 2010 The British Pharmacological Society.en_US
dc.languageengen_US
dc.publisherJohn Wiley & Sons Ltd. The Journal's web site is located at http://www.wiley.com/bw/journal.asp?ref=0007-1188&site=1en_US
dc.relation.ispartofBritish Journal of Pharmacologyen_US
dc.subjectChemopreventionen_US
dc.subjectColitisen_US
dc.subjectColon Carcinogenesisen_US
dc.subjectResveratrol Derivativesen_US
dc.title2,3′,4,4′,5′-Pentamethoxy-trans-stilbene, a resveratrol derivative, inhibits colitis-associated colorectal carcinogenesis in miceen_US
dc.typeArticleen_US
dc.identifier.emailWang, M: mfwang@hku.hken_US
dc.identifier.authorityWang, M=rp00800en_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1111/j.1476-5381.2010.00785.xen_US
dc.identifier.pmid20590626-
dc.identifier.scopuseid_2-s2.0-77954036696en_US
dc.identifier.hkuros176025-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-77954036696&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume160en_US
dc.identifier.issue6en_US
dc.identifier.spage1352en_US
dc.identifier.epage1361en_US
dc.identifier.isiWOS:000279158600008-
dc.publisher.placeUnited Kingdomen_US
dc.identifier.scopusauthoridLi, H=25958185900en_US
dc.identifier.scopusauthoridWu, WKK=18345422600en_US
dc.identifier.scopusauthoridLi, ZJ=35170171500en_US
dc.identifier.scopusauthoridChan, KM=13806480000en_US
dc.identifier.scopusauthoridWong, CCM=26421493300en_US
dc.identifier.scopusauthoridYe, CG=36104628400en_US
dc.identifier.scopusauthoridYu, L=16314581700en_US
dc.identifier.scopusauthoridSung, JJY=35405352400en_US
dc.identifier.scopusauthoridCho, CH=14067000400en_US
dc.identifier.scopusauthoridWang, M=7406691844en_US

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