Academic Journal
Effects of the CK2 inhibitors CX-4945 and CX-5011 on drug-resistant cells.
| العنوان: | Effects of the CK2 inhibitors CX-4945 and CX-5011 on drug-resistant cells. |
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| المؤلفون: | Sofia Zanin, Christian Borgo, Cristina Girardi, Sean E O'Brien, Yoshihiko Miyata, Lorenzo A Pinna, Arianna Donella-Deana, Maria Ruzzene |
| المصدر: | PLoS ONE, Vol 7, Iss 11, p e49193 (2012) |
| بيانات النشر: | Public Library of Science (PLoS), 2012. |
| سنة النشر: | 2012 |
| المجموعة: | LCC:Medicine LCC:Science |
| مصطلحات موضوعية: | Medicine, Science |
| الوصف: | 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. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 1932-6203 |
| Relation: | https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23145120/?tool=EBI; https://doaj.org/toc/1932-6203 |
| DOI: | 10.1371/journal.pone.0049193 |
| URL الوصول: | https://doaj.org/article/1628c93d81e54239a1197f03df0b6790 |
| رقم الانضمام: | edsdoj.1628c93d81e54239a1197f03df0b6790 |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 19326203 |
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| DOI: | 10.1371/journal.pone.0049193 |