Artículo
Zalazar, F.; De Luca, P.; Gardner, K.; Figg, W.D.; Meiss, R.; Spallanzani, R.G.; Vallecorsa, P.; Elguero, B.; Cotignola, J.; Vazquez, E.; De Siervi, A. "Low doses of CPS49 and flavopiridol combination as potential treatment for advanced prostate cancer" (2015) Current Pharmaceutical Biotechnology. 16(6):553-563
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Abstract:
Prostate cancer (PCa) still ranks as the second most frequently diagnosed cancer and metastatic castration-resistant prostate cancer (CRPC) is a foremost cause of men cancer death around the world. The aim of this work was to investigate the selectivity and efficacy of new drug combinations for CRPC. We combined three compounds: paclitaxel (PTX: taxane that inhibits microtubule polymerization); 2-(2,4-Difluoro-phenyl)-4,5,6,7-tetrafluoro-1H-isoindole-1,3(2H)-dione (CPS49; redox-reactive thalidomide analog with anti-angiogenic properties) and flavopiridol (flavo: semi-synthetic flavonoid that inhibits cyclin dependent kinases). We assessed CPS49-flavo or -PTX combinations cytotoxicity in a panel of PCa cell lines and PC3 xenografts. We found that CPS49 enhanced flavo or PTX cytotoxicity in human PCa cell lines while showed resistance in a non-tumor cell line. Furthermore, xenografts generated by inoculation of human prostate carcinoma PC3 cells in nu/nu mice showed that CPS49/flavo administration reduced tumor growth both after 2 weeks of co-treatment and after 1 week of pretreatment with a low dose of flavo followed by 2 weeks of co-treatment. PTX and CPS49 combination did not significantly reduce tumor growth in PC3 xenografts. Histological analysis of xenograft PC3 tumor samples from CPS49/flavo combination showed extensive areas of necrosis induced by the treatment. RT-qPCR array containing 23 genes from PC3 cells or PC3 xenografts exposed to CPS49/flavo combination showed that this treatment shut down the expression of several genes involved in adhesion, migration or invasion. In summary, the antitumor activity of CPS49 or flavopiridol was improved by the combination of these compounds and using half dose of that previously reported. Hence, CPS49-flavo combination is a promising new alternative for PCa therapy. © 2015 Bentham Science Publishers.
Registro:
| Documento: | Artículo |
| Título: | Low doses of CPS49 and flavopiridol combination as potential treatment for advanced prostate cancer |
| Autor: | Zalazar, F.; De Luca, P.; Gardner, K.; Figg, W.D.; Meiss, R.; Spallanzani, R.G.; Vallecorsa, P.; Elguero, B.; Cotignola, J.; Vazquez, E.; De Siervi, A. |
| Filiación: | Laboratorio de Oncología Molecular y Nuevos Blancos Terapéuticos, Instituto de Biología y Medi-cina Experimental (IBYME-CONICET, Buenos Aires, Argentina Laboratory of Receptor Biology and Gene Expression, National Cancer Institute, National Institutes of Health, Bethesda, United States Medical Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, United States Departamento de Patología, Academia Nacional de Medicina, Buenos Aires, Argentina Laboratorio de inflamación y cáncer, Departamento de Química Biológica, Universidad de Buenos Aires (UBA), IQUIBICEN - CONI-CET, Buenos Aires, Argentina Laboratorio de Fisiopatología de la Inmunidad Innata, Instituto de Biología y Medicina Experimental (IBYME), Consejo Nacional de Investigaciones Científicas y Técni-cas (CONICET), Argentina |
| Palabras clave: | CPS49; Flavopiridol; Paclitaxel; Preclinical study; Prostate cancer; Xenografts; antineoplastic agent; cps 49; flavopiridol; unclassified drug; antineoplastic agent; CPS 49; drug combination; flavonoid; flavopiridol; piperidine derivative; thalidomide; animal experiment; animal model; animal tissue; antineoplastic activity; apoptosis; Article; cancer staging; cell adhesion; cell invasion; cell migration; cell viability; clonogenic assay; controlled study; cytotoxicity; drug efficacy; histology; human; human cell; low drug dose; male; microscopy; mouse; nonhuman; prostate cancer; real time polymerase chain reaction; reverse transcription polymerase chain reaction; RNA isolation; tumor growth; tumor volume; analogs and derivatives; animal; cell survival; dose response; drug combination; drug effects; nude mouse; pathology; Prostatic Neoplasms; treatment outcome; tumor cell line; Mus; Animals; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Apoptosis; Cell Line, Tumor; Cell Survival; Dose-Response Relationship, Drug; Drug Combinations; Flavonoids; Humans; Male; Mice; Mice, Nude; Piperidines; Prostatic Neoplasms; Thalidomide; Treatment Outcome |
| Año: | 2015 |
| Volumen: | 16 |
| Número: | 6 |
| Página de inicio: | 553 |
| Página de fin: | 563 |
| DOI: | http://dx.doi.org/10.2174/138920101606150407114407 |
| Título revista: | Current Pharmaceutical Biotechnology |
| Título revista abreviado: | Curr. Pharm. Biotechnol. |
| ISSN: | 13892010 |
| CODEN: | CPBUB |
| CAS: | flavopiridol, 131740-09-5, 146426-40-6; thalidomide, 50-35-1; alvocidib; Antineoplastic Agents; CPS 49; Drug Combinations; Flavonoids; Piperidines; Thalidomide |
| Registro: | https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_13892010_v16_n6_p553_Zalazar |
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Citas:
---------- APA ----------
Zalazar, F., De Luca, P., Gardner, K., Figg, W.D., Meiss, R., Spallanzani, R.G., Vallecorsa, P.,..., De Siervi, A. (2015) . Low doses of CPS49 and flavopiridol combination as potential treatment for advanced prostate cancer. Current Pharmaceutical Biotechnology, 16(6), 553-563.http://dx.doi.org/10.2174/138920101606150407114407
---------- CHICAGO ----------
Zalazar, F., De Luca, P., Gardner, K., Figg, W.D., Meiss, R., Spallanzani, R.G., et al. "Low doses of CPS49 and flavopiridol combination as potential treatment for advanced prostate cancer" . Current Pharmaceutical Biotechnology 16, no. 6 (2015) : 553-563.http://dx.doi.org/10.2174/138920101606150407114407
---------- MLA ----------
Zalazar, F., De Luca, P., Gardner, K., Figg, W.D., Meiss, R., Spallanzani, R.G., et al. "Low doses of CPS49 and flavopiridol combination as potential treatment for advanced prostate cancer" . Current Pharmaceutical Biotechnology, vol. 16, no. 6, 2015, pp. 553-563.http://dx.doi.org/10.2174/138920101606150407114407
---------- VANCOUVER ----------
Zalazar, F., De Luca, P., Gardner, K., Figg, W.D., Meiss, R., Spallanzani, R.G., et al. Low doses of CPS49 and flavopiridol combination as potential treatment for advanced prostate cancer. Curr. Pharm. Biotechnol. 2015;16(6):553-563.http://dx.doi.org/10.2174/138920101606150407114407
