8-Chloroadenosine 3',5'-monophosphate as a novel modulator of multidrug resistance

H. Yokozaki, A. Budillon, T. Clair, K. Kelley, K. H. Cowan, C. Rohlff, R. I. Glazer, Y. S. Cho-Chung

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Abstract

Multidrug resistance (MDR) is a major obstacle in the chemotherapy of cancer, 8-chloroadenosine 3',5'-monophosphate (8-Cl-cAMP), a site-selective analog of cAMP, produced a potent growth inhibition in a spectrum of MDR cell lines. The IC50 (concentration inhibiting 50% of cell proliferation) of 8- Cl-cAMP at 6 days ranged from 0.1 to 3.0 μM in both P-glycoprotein (pgp)- associated and pgp-unassociated MDR cells, and the growth inhibition occurred with continued cell viability. Growth inhibition paralleled down-regulation of RIα subunit and catalytic activity of cAMP-dependent protein kinase. 8- Cl-cAMP also provoked the suppression of the promoter activity of the MDR1 gene. These results demonstrate that type I cAMP-dependent protein kinase plays a role in drug resistance and that 8-Cl-cAMP is a novel modulator of multidrug resistance.

Original languageEnglish (US)
Pages (from-to)423-430
Number of pages8
JournalInternational journal of oncology
Volume3
Issue number3
StatePublished - Jan 1 1993

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ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Yokozaki, H., Budillon, A., Clair, T., Kelley, K., Cowan, K. H., Rohlff, C., Glazer, R. I., & Cho-Chung, Y. S. (1993). 8-Chloroadenosine 3',5'-monophosphate as a novel modulator of multidrug resistance. International journal of oncology, 3(3), 423-430.