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Article: In vivo evidence of γ-tocotrienol as a chemosensitizer in the treatment of hormone-refractory prostate cancer

TitleIn vivo evidence of γ-tocotrienol as a chemosensitizer in the treatment of hormone-refractory prostate cancer
Authors
Issue Date2010
PublisherS Karger AG. The Journal's web site is located at http://www.karger.com/PHA
Citation
Pharmacology, 2010, v. 85 n. 4, p. 248-258 How to Cite?
Abstractγ-Tocotrienol (γT3) is known to selectively kill prostate cancer (PCa) cells and to sensitize the cells to docetaxel (DTX)-induced apoptosis. In the present study, the pharmacokinetics of γT3 and the in vivo cytotoxic response of androgen-independent prostate cancer (AIPCa) tumor following γT3 treatment were investigated. Here, we investigated these antitumor effects for PCa tumors in vivo. The pharmacokinetic and tissue distribution of γT3 after exogenous γT3 supplementation were examined. Meanwhile, the response of the tumor to γT3 alone or in combination with DTX were studied by real-time in vivo bioluminescent imaging and by examination of biomarkers associated with cell proliferation and apoptosis. After intraperitoneal injection, γT3 rapidly disappeared from the serum and was selectively deposited in the AIPCa tumor cells. Administration of γT3 alone for 2 weeks resulted in a significant shrinkage of the AIPCa tumors. Meanwhile, further inhibition of the AIPCa tumor growth was achieved by combined treatment of γT3 and DTX (p < 0.002). The in vivo cytotoxic antitumor effects induced by γT3 seem to be associated with a decrease in expression of cell proliferation markers (proliferating cell nuclear antigen, Ki-67 and Id1) and an increase in the rate of cancer cell apoptosis [cleaved caspase 3 and poly(ADP-ribose) polymerase]. Additionally, the combined agents may be more effective at suppressing the invasiveness of AIPCa. Overall, our results indicate that γT3, either alone or in combination with DTX, may provide a treatment strategy that can improve therapeutic efficacy against AIPCa while reducing the toxicity often seen in patients treated with DTX. Copyright © 2010 S. Karger AG, Basel.
Persistent Identifierhttp://hdl.handle.net/10722/149738
ISSN
2015 Impact Factor: 1.533
2015 SCImago Journal Rankings: 0.645
ISI Accession Number ID
Funding AgencyGrant Number
Kuala Lumpur Kepong Berhad
Research Grant CouncilHKU 7314/01M
HKU7490/03M
7470/04M
Funding Information:

We thank P. N. Chang for her initial involvement in this project. This study was supported by a research grant from Kuala Lumpur Kepong Berhad to Davos Life Science and by Research Grant Council grants to Y. C. W. (HKU 7314/01M, HKU7490/03M and 7470/04M).

References
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DC FieldValueLanguage
dc.contributor.authorYap, WNen_US
dc.contributor.authorZaiden, Nen_US
dc.contributor.authorLuk, SYen_US
dc.contributor.authorLee, DTWen_US
dc.contributor.authorLing, MTen_US
dc.contributor.authorWong, YCen_US
dc.contributor.authorYap, YLen_US
dc.date.accessioned2012-06-26T05:57:50Z-
dc.date.available2012-06-26T05:57:50Z-
dc.date.issued2010en_US
dc.identifier.citationPharmacology, 2010, v. 85 n. 4, p. 248-258en_US
dc.identifier.issn0031-7012en_US
dc.identifier.urihttp://hdl.handle.net/10722/149738-
dc.description.abstractγ-Tocotrienol (γT3) is known to selectively kill prostate cancer (PCa) cells and to sensitize the cells to docetaxel (DTX)-induced apoptosis. In the present study, the pharmacokinetics of γT3 and the in vivo cytotoxic response of androgen-independent prostate cancer (AIPCa) tumor following γT3 treatment were investigated. Here, we investigated these antitumor effects for PCa tumors in vivo. The pharmacokinetic and tissue distribution of γT3 after exogenous γT3 supplementation were examined. Meanwhile, the response of the tumor to γT3 alone or in combination with DTX were studied by real-time in vivo bioluminescent imaging and by examination of biomarkers associated with cell proliferation and apoptosis. After intraperitoneal injection, γT3 rapidly disappeared from the serum and was selectively deposited in the AIPCa tumor cells. Administration of γT3 alone for 2 weeks resulted in a significant shrinkage of the AIPCa tumors. Meanwhile, further inhibition of the AIPCa tumor growth was achieved by combined treatment of γT3 and DTX (p < 0.002). The in vivo cytotoxic antitumor effects induced by γT3 seem to be associated with a decrease in expression of cell proliferation markers (proliferating cell nuclear antigen, Ki-67 and Id1) and an increase in the rate of cancer cell apoptosis [cleaved caspase 3 and poly(ADP-ribose) polymerase]. Additionally, the combined agents may be more effective at suppressing the invasiveness of AIPCa. Overall, our results indicate that γT3, either alone or in combination with DTX, may provide a treatment strategy that can improve therapeutic efficacy against AIPCa while reducing the toxicity often seen in patients treated with DTX. Copyright © 2010 S. Karger AG, Basel.en_US
dc.languageengen_US
dc.publisherS Karger AG. The Journal's web site is located at http://www.karger.com/PHAen_US
dc.relation.ispartofPharmacologyen_US
dc.subject.meshAnimalsen_US
dc.subject.meshAntineoplastic Agents - Pharmacokinetics - Therapeutic Useen_US
dc.subject.meshApoptosis - Drug Effectsen_US
dc.subject.meshCadherins - Biosynthesisen_US
dc.subject.meshCell Line, Tumoren_US
dc.subject.meshCell Proliferation - Drug Effectsen_US
dc.subject.meshChromans - Pharmacokinetics - Therapeutic Useen_US
dc.subject.meshDose-Response Relationship, Drugen_US
dc.subject.meshGene Expression Regulation, Neoplastic - Drug Effectsen_US
dc.subject.meshHumansen_US
dc.subject.meshMaleen_US
dc.subject.meshMiceen_US
dc.subject.meshMice, Inbred Balb Cen_US
dc.subject.meshMice, Inbred C57blen_US
dc.subject.meshMice, Nudeen_US
dc.subject.meshNeoplasm Transplantationen_US
dc.subject.meshNeoplasms, Experimental - Drug Therapyen_US
dc.subject.meshProstatic Neoplasms - Drug Therapyen_US
dc.subject.meshTissue Distributionen_US
dc.subject.meshVitamin E - Analogs & Derivatives - Pharmacokinetics - Therapeutic Useen_US
dc.titleIn vivo evidence of γ-tocotrienol as a chemosensitizer in the treatment of hormone-refractory prostate canceren_US
dc.typeArticleen_US
dc.identifier.emailLing, MT:patling@hkucc.hku.hken_US
dc.identifier.emailWong, YC:ycwong@hkucc.hku.hken_US
dc.identifier.authorityLing, MT=rp00449en_US
dc.identifier.authorityWong, YC=rp00316en_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1159/000278205en_US
dc.identifier.pmid20375535-
dc.identifier.scopuseid_2-s2.0-77950327415en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-77950327415&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume85en_US
dc.identifier.issue4en_US
dc.identifier.spage248en_US
dc.identifier.epage258en_US
dc.identifier.isiWOS:000277110500008-
dc.publisher.placeSwitzerlanden_US
dc.relation.projectThe role of <I>Id-1</I> gene in prostate carcinogenesis and its relationship to invasiveness of prostate cancer-
dc.identifier.scopusauthoridYap, WN=25637949100en_US
dc.identifier.scopusauthoridZaiden, N=8360274200en_US
dc.identifier.scopusauthoridLuk, SY=36243914500en_US
dc.identifier.scopusauthoridLee, DTW=7406666118en_US
dc.identifier.scopusauthoridLing, MT=7102229780en_US
dc.identifier.scopusauthoridWong, YC=7403041798en_US
dc.identifier.scopusauthoridYap, YL=7005551975en_US

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