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Article: 2,3′,4,4′,5′-Pentamethoxy-trans-stilbene, a resveratrol derivative, is a potent inducer of apoptosis in colon cancer cells via targeting microtubules

Title2,3′,4,4′,5′-Pentamethoxy-trans-stilbene, a resveratrol derivative, is a potent inducer of apoptosis in colon cancer cells via targeting microtubules
Authors
KeywordsApoptosis
Colon cancer
Microtubule
Polymethoxystilbene
Resveratrol
Issue Date2009
PublisherElsevier Inc. The Journal's web site is located at http://www.elsevier.com/locate/biochempharm
Citation
Biochemical Pharmacology, 2009, v. 78 n. 9, p. 1224-1232 How to Cite?
AbstractResveratrol, a naturally occurring polyphenolic antioxidant, is a compound holding promise for cancer chemoprevention. Previous studies suggest that 2,3′,4,5′-tetramethoxy-trans-stilbene (TMS) and 3,4,4′,5,-tetramethoxy-trans-stilbene (MR-4), both of which are derivatives of resveratrol, are potent apoptosis-inducing agents with clinical potential. In this study, we chemically synthesized 2,3′,4,4′,5′-pentamethoxy-trans-stilbene (PMS), the hybrid molecule of TMS and MR-4, and determined its effects on colon cancer growth. When compared with its parent compounds, PMS displayed more potent in vitro anti-mitogenic effect on colon cancer cells (Caco-2, HT-29 and SW1116). Moreover, PMS inhibited tumor growth in vivo in a colon cancer xenograft model. In this connection, PMS strongly induced apoptosis in HT-29 cells as evidenced by increased PARP cleavage, DNA fragmentation, and accumulation of sub-G 1 population. Further mechanistic analysis revealed that PMS enhanced the polymerization of microtubules, which was followed by G 2/M mitotic arrest and caspase-dependent apoptosis. The activation of caspases-3, -7, -8, and -9 was involved in PMS-induced apoptosis with concomitant down-regulation of the pro-survival PI3K/Akt signaling. Collectively, these data suggest that PMS is a potent inducer of apoptosis via targeting microtubules and may merit investigation as a potential chemoprophylactic and therapeutic agent for colon cancer. © 2009 Elsevier Inc. All rights reserved.
Persistent Identifierhttp://hdl.handle.net/10722/89298
ISSN
2015 Impact Factor: 5.091
2015 SCImago Journal Rankings: 2.263
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorLi, Hen_HK
dc.contributor.authorWu, WKKen_HK
dc.contributor.authorZheng, Zen_HK
dc.contributor.authorChe, CTen_HK
dc.contributor.authorYu, Len_HK
dc.contributor.authorLi, ZJen_HK
dc.contributor.authorWu, YCen_HK
dc.contributor.authorCheng, KWen_HK
dc.contributor.authorYu, Jen_HK
dc.contributor.authorCho, CHen_HK
dc.contributor.authorWang, Men_HK
dc.date.accessioned2010-09-06T09:55:05Z-
dc.date.available2010-09-06T09:55:05Z-
dc.date.issued2009en_HK
dc.identifier.citationBiochemical Pharmacology, 2009, v. 78 n. 9, p. 1224-1232en_HK
dc.identifier.issn0006-2952en_HK
dc.identifier.urihttp://hdl.handle.net/10722/89298-
dc.description.abstractResveratrol, a naturally occurring polyphenolic antioxidant, is a compound holding promise for cancer chemoprevention. Previous studies suggest that 2,3′,4,5′-tetramethoxy-trans-stilbene (TMS) and 3,4,4′,5,-tetramethoxy-trans-stilbene (MR-4), both of which are derivatives of resveratrol, are potent apoptosis-inducing agents with clinical potential. In this study, we chemically synthesized 2,3′,4,4′,5′-pentamethoxy-trans-stilbene (PMS), the hybrid molecule of TMS and MR-4, and determined its effects on colon cancer growth. When compared with its parent compounds, PMS displayed more potent in vitro anti-mitogenic effect on colon cancer cells (Caco-2, HT-29 and SW1116). Moreover, PMS inhibited tumor growth in vivo in a colon cancer xenograft model. In this connection, PMS strongly induced apoptosis in HT-29 cells as evidenced by increased PARP cleavage, DNA fragmentation, and accumulation of sub-G 1 population. Further mechanistic analysis revealed that PMS enhanced the polymerization of microtubules, which was followed by G 2/M mitotic arrest and caspase-dependent apoptosis. The activation of caspases-3, -7, -8, and -9 was involved in PMS-induced apoptosis with concomitant down-regulation of the pro-survival PI3K/Akt signaling. Collectively, these data suggest that PMS is a potent inducer of apoptosis via targeting microtubules and may merit investigation as a potential chemoprophylactic and therapeutic agent for colon cancer. © 2009 Elsevier Inc. All rights reserved.en_HK
dc.languageengen_HK
dc.publisherElsevier Inc. The Journal's web site is located at http://www.elsevier.com/locate/biochempharmen_HK
dc.relation.ispartofBiochemical Pharmacologyen_HK
dc.subjectApoptosisen_HK
dc.subjectColon canceren_HK
dc.subjectMicrotubuleen_HK
dc.subjectPolymethoxystilbeneen_HK
dc.subjectResveratrolen_HK
dc.subject.meshApoptosis - drug effects-
dc.subject.meshColonic Neoplasms - enzymology - pathology-
dc.subject.meshMicrotubules - drug effects-
dc.subject.meshStilbenes - pharmacology-
dc.subject.meshResveratrol-
dc.title2,3′,4,4′,5′-Pentamethoxy-trans-stilbene, a resveratrol derivative, is a potent inducer of apoptosis in colon cancer cells via targeting microtubulesen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0006-2952&volume=78&issue=9&spage=1224&epage=1232&date=2009&atitle=2,3′,4,4′,5′-Pentamethoxy-trans-stilbene,+a+resveratrol+derivative,+is+a+potent+inducer+of+apoptosis+in+colon+cancer+cells+via+targeting+microtubulesen_HK
dc.identifier.emailWang, M: mfwang@hku.hken_HK
dc.identifier.authorityWang, M=rp00800en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1016/j.bcp.2009.06.109en_HK
dc.identifier.pmid19591809-
dc.identifier.scopuseid_2-s2.0-70249113671en_HK
dc.identifier.hkuros169741en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-70249113671&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume78en_HK
dc.identifier.issue9en_HK
dc.identifier.spage1224en_HK
dc.identifier.epage1232en_HK
dc.identifier.isiWOS:000270483000015-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridLi, H=25958185900en_HK
dc.identifier.scopusauthoridWu, WKK=7407080904en_HK
dc.identifier.scopusauthoridZheng, Z=8451746600en_HK
dc.identifier.scopusauthoridChe, CT=7102442768en_HK
dc.identifier.scopusauthoridYu, L=16314581700en_HK
dc.identifier.scopusauthoridLi, ZJ=35170171500en_HK
dc.identifier.scopusauthoridWu, YC=24469365700en_HK
dc.identifier.scopusauthoridCheng, KW=12141247000en_HK
dc.identifier.scopusauthoridYu, J=35351306800en_HK
dc.identifier.scopusauthoridCho, CH=14067000400en_HK
dc.identifier.scopusauthoridWang, M=7406691844en_HK
dc.identifier.citeulike5367173-

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