Effects of the CK2 inhibitors CX-4945 and CX-5011 on drug-resistant cells.

CK2 is a pleiotropic protein kinase, which regulates many survival pathways and plays a global anti-apoptotic function. It is highly expressed in tumor cells, and is presently considered a promising therapeutic target. Among the many inhibitors available for this kinase, the recently developed CX-49...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Sofia Zanin, Christian Borgo, Cristina Girardi, Sean E O'Brien, Yoshihiko Miyata, Lorenzo A Pinna, Arianna Donella-Deana, Maria Ruzzene
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/1628c93d81e54239a1197f03df0b6790
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:1628c93d81e54239a1197f03df0b6790
record_format	dspace
spelling	oai:doaj.org-article:1628c93d81e54239a1197f03df0b67902021-11-18T08:09:20ZEffects of the CK2 inhibitors CX-4945 and CX-5011 on drug-resistant cells.1932-620310.1371/journal.pone.0049193https://doaj.org/article/1628c93d81e54239a1197f03df0b67902012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23145120/?tool=EBIhttps://doaj.org/toc/1932-6203CK2 is a pleiotropic protein kinase, which regulates many survival pathways and plays a global anti-apoptotic function. It is highly expressed in tumor cells, and is presently considered a promising therapeutic target. Among the many inhibitors available for this kinase, the recently developed CX-4945 and CX-5011 have proved to be very potent, selective and effective in inducing cell death in tumor cells; CX-4945 has recently entered clinical trials. However, no data are available on the efficacy of these compounds to overcome drug resistance, a major reasons of cancer therapy failure. Here we address this point, by studying their effects in several tumor cell lines, each available as variant R resistant to drug-induced apoptosis, and normal-sensitive variant S. We found that the inhibition of endogenous CK2 was very similar in S and R treated cells, with more than 50% CK2 activity reduction at sub-micromolar concentrations of CX-4945 and CX-5011. A consequent apoptotic response was induced both in S and R variants of each pairs. Moreover, the combined treatment of CX-4945 plus vinblastine was able to sensitize to vinblastine R cells that are otherwise almost insensitive to this conventional antitumor drug. Consistently, doxorubicin accumulation in multidrug resistant (MDR) cells was greatly increased by CX-4945.In summary, we demonstrated that all the R variants are sensitive to CX-4945 and CX-5011; since some of the treated R lines express the extrusion pump Pgp, often responsible of the MDR phenotype, we can also conclude that the two inhibitors can successfully overcome the MDR phenomenon.Sofia ZaninChristian BorgoCristina GirardiSean E O'BrienYoshihiko MiyataLorenzo A PinnaArianna Donella-DeanaMaria RuzzenePublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 11, p e49193 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Sofia Zanin Christian Borgo Cristina Girardi Sean E O'Brien Yoshihiko Miyata Lorenzo A Pinna Arianna Donella-Deana Maria Ruzzene Effects of the CK2 inhibitors CX-4945 and CX-5011 on drug-resistant cells.
description	CK2 is a pleiotropic protein kinase, which regulates many survival pathways and plays a global anti-apoptotic function. It is highly expressed in tumor cells, and is presently considered a promising therapeutic target. Among the many inhibitors available for this kinase, the recently developed CX-4945 and CX-5011 have proved to be very potent, selective and effective in inducing cell death in tumor cells; CX-4945 has recently entered clinical trials. However, no data are available on the efficacy of these compounds to overcome drug resistance, a major reasons of cancer therapy failure. Here we address this point, by studying their effects in several tumor cell lines, each available as variant R resistant to drug-induced apoptosis, and normal-sensitive variant S. We found that the inhibition of endogenous CK2 was very similar in S and R treated cells, with more than 50% CK2 activity reduction at sub-micromolar concentrations of CX-4945 and CX-5011. A consequent apoptotic response was induced both in S and R variants of each pairs. Moreover, the combined treatment of CX-4945 plus vinblastine was able to sensitize to vinblastine R cells that are otherwise almost insensitive to this conventional antitumor drug. Consistently, doxorubicin accumulation in multidrug resistant (MDR) cells was greatly increased by CX-4945.In summary, we demonstrated that all the R variants are sensitive to CX-4945 and CX-5011; since some of the treated R lines express the extrusion pump Pgp, often responsible of the MDR phenotype, we can also conclude that the two inhibitors can successfully overcome the MDR phenomenon.
format	article
author	Sofia Zanin Christian Borgo Cristina Girardi Sean E O'Brien Yoshihiko Miyata Lorenzo A Pinna Arianna Donella-Deana Maria Ruzzene
author_facet	Sofia Zanin Christian Borgo Cristina Girardi Sean E O'Brien Yoshihiko Miyata Lorenzo A Pinna Arianna Donella-Deana Maria Ruzzene
author_sort	Sofia Zanin
title	Effects of the CK2 inhibitors CX-4945 and CX-5011 on drug-resistant cells.
title_short	Effects of the CK2 inhibitors CX-4945 and CX-5011 on drug-resistant cells.
title_full	Effects of the CK2 inhibitors CX-4945 and CX-5011 on drug-resistant cells.
title_fullStr	Effects of the CK2 inhibitors CX-4945 and CX-5011 on drug-resistant cells.
title_full_unstemmed	Effects of the CK2 inhibitors CX-4945 and CX-5011 on drug-resistant cells.
title_sort	effects of the ck2 inhibitors cx-4945 and cx-5011 on drug-resistant cells.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/1628c93d81e54239a1197f03df0b6790
work_keys_str_mv	AT sofiazanin effectsoftheck2inhibitorscx4945andcx5011ondrugresistantcells AT christianborgo effectsoftheck2inhibitorscx4945andcx5011ondrugresistantcells AT cristinagirardi effectsoftheck2inhibitorscx4945andcx5011ondrugresistantcells AT seaneobrien effectsoftheck2inhibitorscx4945andcx5011ondrugresistantcells AT yoshihikomiyata effectsoftheck2inhibitorscx4945andcx5011ondrugresistantcells AT lorenzoapinna effectsoftheck2inhibitorscx4945andcx5011ondrugresistantcells AT ariannadonelladeana effectsoftheck2inhibitorscx4945andcx5011ondrugresistantcells AT mariaruzzene effectsoftheck2inhibitorscx4945andcx5011ondrugresistantcells
_version_	1718422090701340672

Effects of the CK2 inhibitors CX-4945 and CX-5011 on drug-resistant cells.

Ejemplares similares