Article: Evidence of a novel docetaxel sensitizer, garlic-derived S-allylmercaptocysteine, as a treatment option for hormone refractory prostate cancer

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TitleEvidence of a novel docetaxel sensitizer, garlic-derived S-allylmercaptocysteine, as a treatment option for hormone refractory prostate cancer
AuthorsHoward, EW1
Lee, DT1
Yung, TC1
Chee, WC1
Wang, X1
Yong, CW1
Issue Date2008
PublisherJohn Wiley & Sons, Inc.. The Journal's web site is located at http://www3.interscience.wiley.com/journal/29331/home
CitationInternational Journal Of Cancer, 2008, v. 122 n. 9, p. 1941-1948 [How to Cite?]
DOI: http://dx.doi.org/10.1002/ijc.23355
AbstractThe recent introduction of docetaxel in the treatment of hormone refractory prostate cancer (HRPC) has made a small but significant impact on patient survival. However, its effect is limited by intolerance and resistance. The aim of our study was to investigate if the garlic-derived compound, S-allylmercaptocysteine (SAMC), was able to act as a docetaxel sensitizing agent. First, the effect of SAMC on docetaxel sensitivity was examined on 3 HRPC cell lines by colony forming assay. We found that SAMC increased the efficacy of docetaxel on colony forming inhibition by 9-50% compared to single agent treatment. Second, using the HRPC CWR22R nude mice model, we found that the combination of SAMC and docetaxel was 53% more potent than docetaxel alone (p = 0.037). In addition, there was no additive toxicity in the mice treated with the combination therapy evidenced by histological and functional analysis of liver, kidney and bone marrow. These results suggest that SAMC is able to increase the anticancer effect of docetaxel without causing additional toxic effect in vivo. Third, flow cytometry and Western blotting analysis on HRPC cell lines demonstrated that SAMC promoted docetaxel-induced G2/M phase cell cycle arrest and apoptotic induction. In addition, immunohistochemistry on CWR22R xenograft revealed a suppression of Bcl-2 expression and upregulation of E-cadherin in the SAMC and docetaxel treated animals. These results suggest that SAMC may promote docetaxel-induced cell death through promoting G2/M cell cycle arrest and apoptosis. Our study implies a potential role for SAMC in improving docetaxel based chemotherapy for the treatment of HRPC. © 2008 Wiley-Liss, Inc.
ISSN0020-7136
2011 Impact Factor: 5.444
2011 SCImago Journal Rankings: 0.620
DOIhttp://dx.doi.org/10.1002/ijc.23355
ISI Accession Number IDWOS:000254224100004
ReferencesReferences in Scopus
DC Field
Value
dc.contributor.authorHoward, EW
dc.contributor.authorLee, DT
dc.contributor.authorYung, TC
dc.contributor.authorChee, WC
dc.contributor.authorWang, X
dc.contributor.authorYong, CW
dc.date.accessioned2010-09-06T05:58:46Z
dc.date.available2010-09-06T05:58:46Z
dc.date.issued2008
dc.description.abstractThe recent introduction of docetaxel in the treatment of hormone refractory prostate cancer (HRPC) has made a small but significant impact on patient survival. However, its effect is limited by intolerance and resistance. The aim of our study was to investigate if the garlic-derived compound, S-allylmercaptocysteine (SAMC), was able to act as a docetaxel sensitizing agent. First, the effect of SAMC on docetaxel sensitivity was examined on 3 HRPC cell lines by colony forming assay. We found that SAMC increased the efficacy of docetaxel on colony forming inhibition by 9-50% compared to single agent treatment. Second, using the HRPC CWR22R nude mice model, we found that the combination of SAMC and docetaxel was 53% more potent than docetaxel alone (p = 0.037). In addition, there was no additive toxicity in the mice treated with the combination therapy evidenced by histological and functional analysis of liver, kidney and bone marrow. These results suggest that SAMC is able to increase the anticancer effect of docetaxel without causing additional toxic effect in vivo. Third, flow cytometry and Western blotting analysis on HRPC cell lines demonstrated that SAMC promoted docetaxel-induced G2/M phase cell cycle arrest and apoptotic induction. In addition, immunohistochemistry on CWR22R xenograft revealed a suppression of Bcl-2 expression and upregulation of E-cadherin in the SAMC and docetaxel treated animals. These results suggest that SAMC may promote docetaxel-induced cell death through promoting G2/M cell cycle arrest and apoptosis. Our study implies a potential role for SAMC in improving docetaxel based chemotherapy for the treatment of HRPC. © 2008 Wiley-Liss, Inc.
dc.description.natureLink_to_subscribed_fulltext
dc.identifier.citationInternational Journal Of Cancer, 2008, v. 122 n. 9, p. 1941-1948 [How to Cite?]
DOI: http://dx.doi.org/10.1002/ijc.23355
dc.identifier.doihttp://dx.doi.org/10.1002/ijc.23355
dc.identifier.epage1948
dc.identifier.hkuros147327
dc.identifier.isiWOS:000254224100004
dc.identifier.issn0020-7136
2011 Impact Factor: 5.444
2011 SCImago Journal Rankings: 0.620
dc.identifier.issue9
dc.identifier.openurl
dc.identifier.pmid18183597
dc.identifier.scopuseid_2-s2.0-40749160978
dc.identifier.spage1941
dc.identifier.urihttp://hdl.handle.net/10722/67843
dc.identifier.volume122
dc.languageeng
dc.publisherJohn Wiley & Sons, Inc.. The Journal's web site is located at http://www3.interscience.wiley.com/journal/29331/home
dc.publisher.placeUnited States
dc.relation.ispartofInternational Journal of Cancer
dc.relation.referencesReferences in Scopus
dc.rightsInternational Journal of Cancer. Copyright © John Wiley & Sons, Inc.
dc.subject.meshAnimals
dc.subject.meshAntineoplastic Combined Chemotherapy Protocols - adverse effects - pharmacology
dc.subject.meshApoptosis - drug effects
dc.subject.meshBlotting, Western
dc.subject.meshCadherins - metabolism
dc.subject.meshCell Division - drug effects
dc.subject.meshCell Line, Tumor
dc.subject.meshCysteine - adverse effects - analogs & derivatives - pharmacology
dc.subject.meshDown-Regulation - drug effects
dc.subject.meshDrug Synergism
dc.subject.meshFlow Cytometry
dc.subject.meshG2 Phase - drug effects
dc.subject.meshGarlic
dc.subject.meshGene Expression Regulation, Neoplastic - drug effects
dc.subject.meshHumans
dc.subject.meshImmunohistochemistry
dc.subject.meshMale
dc.subject.meshMice
dc.subject.meshMice, Nude
dc.subject.meshNeoplasms, Experimental - drug therapy - metabolism
dc.subject.meshProstatic Neoplasms - drug therapy - metabolism
dc.subject.meshProto-Oncogene Proteins c-bcl-2 - metabolism
dc.subject.meshTaxoids - adverse effects - pharmacology
dc.subject.meshTransplantation, Heterologous
dc.subject.meshTumor Stem Cell Assay
dc.subject.meshUp-Regulation - drug effects
dc.titleEvidence of a novel docetaxel sensitizer, garlic-derived S-allylmercaptocysteine, as a treatment option for hormone refractory prostate cancer
dc.typeArticle
Author Affiliations
  1. The University of Hong Kong