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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Publicado:	2015
Materias:	CPS49 Flavopiridol Paclitaxel Preclinical study Prostate cancer Xenografts antineoplastic agent cps 49 flavopiridol unclassified drug CPS 49 drug combination flavonoid 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 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 Thalidomide Treatment Outcome
Acceso en línea:	https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_13892010_v16_n6_p553_Zalazar http://hdl.handle.net/20.500.12110/paper_13892010_v16_n6_p553_Zalazar
Aporte de:	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) de Universidad de Buenos Aires

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spelling	paper:paper_13892010_v16_n6_p553_Zalazar2023-06-08T16:13:07Z Low doses of CPS49 and flavopiridol combination as potential treatment for advanced prostate cancer 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 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. 2015 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_13892010_v16_n6_p553_Zalazar http://hdl.handle.net/20.500.12110/paper_13892010_v16_n6_p553_Zalazar
institution	Universidad de Buenos Aires
institution_str	I-28
repository_str	R-134
collection	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA)
topic	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
spellingShingle	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 Low doses of CPS49 and flavopiridol combination as potential treatment for advanced prostate cancer
topic_facet	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
description	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.
title	Low doses of CPS49 and flavopiridol combination as potential treatment for advanced prostate cancer
title_short	Low doses of CPS49 and flavopiridol combination as potential treatment for advanced prostate cancer
title_full	Low doses of CPS49 and flavopiridol combination as potential treatment for advanced prostate cancer
title_fullStr	Low doses of CPS49 and flavopiridol combination as potential treatment for advanced prostate cancer
title_full_unstemmed	Low doses of CPS49 and flavopiridol combination as potential treatment for advanced prostate cancer
title_sort	low doses of cps49 and flavopiridol combination as potential treatment for advanced prostate cancer
publishDate	2015
url	https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_13892010_v16_n6_p553_Zalazar http://hdl.handle.net/20.500.12110/paper_13892010_v16_n6_p553_Zalazar
_version_	1768545108136820736

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

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