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

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

Research output: Contribution to journalArticle

22 Citations (Scopus)

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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Multiple Drug Resistance
P-Glycoprotein
Cyclic AMP-Dependent Protein Kinases
Growth
Drug Resistance
Inhibitory Concentration 50
Catalytic Domain
Cell Survival
Down-Regulation
Cell Proliferation
8-chloro-cyclic adenosine monophosphate
Drug Therapy
Cell Line
Genes
Neoplasms

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Yokozaki, H., Budillon, A., Clair, T., Kelley, K., Cowan, K. H., Rohlff, C., ... 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.

8-Chloroadenosine 3',5'-monophosphate as a novel modulator of multidrug resistance. / Yokozaki, H.; Budillon, A.; Clair, T.; Kelley, K.; Cowan, Kenneth H; Rohlff, C.; Glazer, R. I.; Cho-Chung, Y. S.

In: International journal of oncology, Vol. 3, No. 3, 01.01.1993, p. 423-430.

Research output: Contribution to journalArticle

Yokozaki, H, Budillon, A, Clair, T, Kelley, K, Cowan, KH, Rohlff, C, Glazer, RI & Cho-Chung, YS 1993, '8-Chloroadenosine 3',5'-monophosphate as a novel modulator of multidrug resistance', International journal of oncology, vol. 3, no. 3, pp. 423-430.
Yokozaki H, Budillon A, Clair T, Kelley K, Cowan KH, Rohlff C et al. 8-Chloroadenosine 3',5'-monophosphate as a novel modulator of multidrug resistance. International journal of oncology. 1993 Jan 1;3(3):423-430.
Yokozaki, H. ; Budillon, A. ; Clair, T. ; Kelley, K. ; Cowan, Kenneth H ; Rohlff, C. ; Glazer, R. I. ; Cho-Chung, Y. S. / 8-Chloroadenosine 3',5'-monophosphate as a novel modulator of multidrug resistance. In: International journal of oncology. 1993 ; Vol. 3, No. 3. pp. 423-430.
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