Targeting Bcl-2 Protein to Enhance Chemosensitivity of Hormone Refractory Prostate Cancer Cell Line, DU-145 by a Synergistic Combination of Docetaxel and Gossypol.
Objective: Docetaxel has become the standard of care for hormone-refractory prostate cancer (HRPC), however drug resistance and toxicity are still challenging in daily cancer practice. The anti-apoptotic pathway centered around the Bcl-2 protein might be one of the responsible pathways. Adding a sec...
| Publicado en: | Turkiye Klinikleri Journal of Medical Sciences Vol. 31; no. 4; pp. 859 - 867 |
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| Autores principales: | , , , , , |
| Formato: | pictorial research tables/charts Journal Article |
| Publicado: |
Turkiye Klinikleri
Aug2011
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=104636553&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 104636553 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 13000292 1VOP jtl: Turkiye Klinikleri Journal of Medical Sciences issn: 13000292 maglogo: N pubinfo: dt: Aug2011 vid: 31 iid: 4 pid: 67298 pub: Turkiye Klinikleri artinfo: ui: 104636553 104636553 2011333737 10.5336/medsci.2010-19849 104636553 ppf: 859 ppct: 8 formats: fmt: @attributes: type: P tig: atl: Targeting Bcl-2 Protein to Enhance Chemosensitivity of Hormone Refractory Prostate Cancer Cell Line, DU-145 by a Synergistic Combination of Docetaxel and Gossypol. aug: au: Uzunoglu, Selim Karaca, Burçak Atmaca, Harika Kisim, Asli Karabulut, Bülent Uslu, Rüçhan sug: subj: Antineoplastic Agents Therapeutic Use Docetaxel Therapeutic Use Prostatic Neoplasms Drug Therapy Proteins Apoptosis Blotting, Western Data Analysis Software Descriptive Statistics Enzyme-Linked Immunosorbent Assay Human In Vitro Studies Paired T-Tests Tissue Culture Techniques ab: Objective: Docetaxel has become the standard of care for hormone-refractory prostate cancer (HRPC), however drug resistance and toxicity are still challenging in daily cancer practice. The anti-apoptotic pathway centered around the Bcl-2 protein might be one of the responsible pathways. Adding a second drug to docetaxel treatment is one of the most common approaches to solve this problem. Gossypol was reported to have potent anticancer activities in prostate cancer. In this study, we searched for the possible synergistic cytotoxic/apoptotic effects of this combination treatment in hormone- and drug resistant prostate cancer cell line, DU-145 via inhibition of Bcl-2 protein. Material and Methods: XTT cell viability assay was used to assess cytotoxicity of the drugs alone and in combination. For verifying apoptosis, Cell Death Detection Elisa Plus Kit and Caspase-Glo 3/7 assay were used. Western Blot analysis for Bcl-2 protein was carried out. Results: A novel drug combination of docetaxel and gossypol resulted in a significant synergistic cytotoxic activity and apoptosis as compared to any single agent alone, in a dose- and time dependent manner, and also significantly reduced Bcl-2 protein levels in DU-145, in doses that can be used clinically. Conclusion: Adding gossypol to docetaxel as a combination treatment in HRPC patients might be a solution for taxane resistant patients. Inhibition of Bcl-2 might be one of the underlying routes of activity for this combination. pubtype: Academic Journal doctype: pictorial research tables/charts Journal Article ougenre: Article language: Turkish refInfo: holdings: @attributes: islocal: N |
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