Low doses of CPS49 and flavopiridol combination as potential treatment for advanced prostate cancer

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...

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Autor principal: Zalazar, F.
Otros Autores: De Luca, P., Gardner, K., Figg, W.D, Meiss, R., Spallanzani, R.G, Vallecorsa, P., Elguero, B., Cotignola, J., Vazquez, E., De Siervi, A.
Formato: Capítulo de libro
Lenguaje:Inglés
Publicado: Bentham Science Publishers B.V. 2015
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Acceso en línea:Registro en Scopus
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024 7 |2 scopus  |a 2-s2.0-84928944531 
024 7 |2 cas  |a flavopiridol, 131740-09-5, 146426-40-6; thalidomide, 50-35-1; alvocidib; Antineoplastic Agents; CPS 49; Drug Combinations; Flavonoids; Piperidines; Thalidomide 
040 |a Scopus  |b spa  |c AR-BaUEN  |d AR-BaUEN 
030 |a CPBUB 
100 1 |a Zalazar, F. 
245 1 0 |a Low doses of CPS49 and flavopiridol combination as potential treatment for advanced prostate cancer 
260 |b Bentham Science Publishers B.V.  |c 2015 
270 1 0 |m De Siervi, A.; Laboratorio de Oncología Molecular y Nuevos Blancos Terapéuticos (IBYME-CONICET), Vuelta de Obligado 2490, Argentina 
506 |2 openaire  |e Política editorial 
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504 |a Kentepozidis, N., Soultati, A., Giassas, S., Vardakis, N., Kalykaki, A., Kotsakis, A., Papadimitraki, E., Georgoulias, V., Paclitaxel in combination with carboplatin as salvage treatment in patients with castration-resistant prostate cancer: A Hellenic oncology research group multicenter phase II study (2012) Cancer Chemother. Pharmacol., 70, pp. 161-168 
504 |a Jeske, S., Tagawa, S.T., Olowokure, O., Selzer, J., Giannakakou, P., Nanus, D.M., Carboplatin plus paclitaxel therapy after docetaxel in men with metastatic castrate resistant prostate cancer (2011) Urol Oncol., 29, pp. 676-681 
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504 |a Senderowicz, A.M., Small-molecule cyclin-dependent kinase modulators (2003) Oncogene, 22, pp. 6609-6620 
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504 |a Dai, Y., Grant, S., Cyclin-dependent kinase inhibitors (2003) Curr. Opin. Pharmacol., 3, pp. 362-370 
504 |a Newcomb, E.W., Flavopiridol: Pleiotropic biological effects enhance its anti-cancer activity (2004) Anticancer Drugs, 15, pp. 411-419 
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504 |a De Luca, P., Vazquez, E.S., Moiola, C.P., Zalazar, F., Cotignola, J., Gueron, G., Gardner, K., De Siervi, A., BRCA1 loss induces GADD153-mediated doxorubicin resistance in prostate cancer (2011) Mol. Cancer Res., 9, pp. 1078-1090 
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504 |a Jiao, W., Lin, H.M., Datta, J., Braunschweig, T., Chung, J.Y., Hewitt, S.M., Rane, S.G., Aberrant nucleocytoplasmic localization of the retinoblastoma tumor suppressor protein in human cancer correlates with moderate/poor tumor differentiation (2008) Oncogene, 27, pp. 3156-3164 
504 |a Chen, Y.M., Shih, J.F., Lee, C.S., Chen, M.C., Lin, W.C., Tsai, C.M., Perng, R.P., Phase II study of docetaxel and ifosfamide combination chemotherapy in non-small-cell lung cancer patients failing previous chemotherapy with or without paclitaxel (2003) Lung Cancer, 39, pp. 209-214 
520 3 |a 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.  |l eng 
593 |a Laboratorio de Oncología Molecular y Nuevos Blancos Terapéuticos, Instituto de Biología y Medi-cina Experimental (IBYME-CONICET, Buenos Aires, Argentina 
593 |a Laboratory of Receptor Biology and Gene Expression, National Cancer Institute, National Institutes of Health, Bethesda, United States 
593 |a Medical Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, United States 
593 |a Departamento de Patología, Academia Nacional de Medicina, Buenos Aires, Argentina 
593 |a Laboratorio de inflamación y cáncer, Departamento de Química Biológica, Universidad de Buenos Aires (UBA), IQUIBICEN - CONI-CET, Buenos Aires, Argentina 
593 |a Laboratorio de Fisiopatología de la Inmunidad Innata, Instituto de Biología y Medicina Experimental (IBYME), Consejo Nacional de Investigaciones Científicas y Técni-cas (CONICET), Argentina 
690 1 0 |a CPS49 
690 1 0 |a FLAVOPIRIDOL 
690 1 0 |a PACLITAXEL 
690 1 0 |a PRECLINICAL STUDY 
690 1 0 |a PROSTATE CANCER 
690 1 0 |a XENOGRAFTS 
690 1 0 |a ANTINEOPLASTIC AGENT 
690 1 0 |a CPS 49 
690 1 0 |a FLAVOPIRIDOL 
690 1 0 |a UNCLASSIFIED DRUG 
690 1 0 |a ANTINEOPLASTIC AGENT 
690 1 0 |a CPS 49 
690 1 0 |a DRUG COMBINATION 
690 1 0 |a FLAVONOID 
690 1 0 |a FLAVOPIRIDOL 
690 1 0 |a PIPERIDINE DERIVATIVE 
690 1 0 |a THALIDOMIDE 
690 1 0 |a ANIMAL EXPERIMENT 
690 1 0 |a ANIMAL MODEL 
690 1 0 |a ANIMAL TISSUE 
690 1 0 |a ANTINEOPLASTIC ACTIVITY 
690 1 0 |a APOPTOSIS 
690 1 0 |a ARTICLE 
690 1 0 |a CANCER STAGING 
690 1 0 |a CELL ADHESION 
690 1 0 |a CELL INVASION 
690 1 0 |a CELL MIGRATION 
690 1 0 |a CELL VIABILITY 
690 1 0 |a CLONOGENIC ASSAY 
690 1 0 |a CONTROLLED STUDY 
690 1 0 |a CYTOTOXICITY 
690 1 0 |a DRUG EFFICACY 
690 1 0 |a HISTOLOGY 
690 1 0 |a HUMAN 
690 1 0 |a HUMAN CELL 
690 1 0 |a LOW DRUG DOSE 
690 1 0 |a MALE 
690 1 0 |a MICROSCOPY 
690 1 0 |a MOUSE 
690 1 0 |a NONHUMAN 
690 1 0 |a PROSTATE CANCER 
690 1 0 |a REAL TIME POLYMERASE CHAIN REACTION 
690 1 0 |a REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION 
690 1 0 |a RNA ISOLATION 
690 1 0 |a TUMOR GROWTH 
690 1 0 |a TUMOR VOLUME 
690 1 0 |a ANALOGS AND DERIVATIVES 
690 1 0 |a ANIMAL 
690 1 0 |a CELL SURVIVAL 
690 1 0 |a DOSE RESPONSE 
690 1 0 |a DRUG COMBINATION 
690 1 0 |a DRUG EFFECTS 
690 1 0 |a NUDE MOUSE 
690 1 0 |a PATHOLOGY 
690 1 0 |a PROSTATIC NEOPLASMS 
690 1 0 |a TREATMENT OUTCOME 
690 1 0 |a TUMOR CELL LINE 
690 1 0 |a MUS 
690 1 0 |a ANIMALS 
690 1 0 |a ANTINEOPLASTIC AGENTS 
690 1 0 |a ANTINEOPLASTIC COMBINED CHEMOTHERAPY PROTOCOLS 
690 1 0 |a APOPTOSIS 
690 1 0 |a CELL LINE, TUMOR 
690 1 0 |a CELL SURVIVAL 
690 1 0 |a DOSE-RESPONSE RELATIONSHIP, DRUG 
690 1 0 |a DRUG COMBINATIONS 
690 1 0 |a FLAVONOIDS 
690 1 0 |a HUMANS 
690 1 0 |a MALE 
690 1 0 |a MICE 
690 1 0 |a MICE, NUDE 
690 1 0 |a PIPERIDINES 
690 1 0 |a PROSTATIC NEOPLASMS 
690 1 0 |a THALIDOMIDE 
690 1 0 |a TREATMENT OUTCOME 
653 0 0 |a cps 49 
700 1 |a De Luca, P. 
700 1 |a Gardner, K. 
700 1 |a Figg, W.D. 
700 1 |a Meiss, R. 
700 1 |a Spallanzani, R.G. 
700 1 |a Vallecorsa, P. 
700 1 |a Elguero, B. 
700 1 |a Cotignola, J. 
700 1 |a Vazquez, E. 
700 1 |a De Siervi, A. 
773 0 |d Bentham Science Publishers B.V., 2015  |g v. 16  |h pp. 553-563  |k n. 6  |p Curr. Pharm. Biotechnol.  |x 13892010  |t Current Pharmaceutical Biotechnology 
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856 4 0 |u https://doi.org/10.2174/138920101606150407114407  |y DOI 
856 4 0 |u https://hdl.handle.net/20.500.12110/paper_13892010_v16_n6_p553_Zalazar  |y Handle 
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