title: 8-chloroadenosine 3',5'-monophosphate as a novel modulator of multidrug-resistance.
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 muM 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 RIalpha 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.
authors.affiliation: NCI,TUMOR IMMUNOL & BIOL LAB,CELLULAR BIOCHEM SECT,BLDG 10,RM 5B38,BETHESDA,MD 20892. NCI,MED BRANCH,BETHESDA,MD 20892. GEORGETOWN UNIV,DEPT PHARMACOL,WASHINGTON,DC 20007.
authors.forename: H
authors.initials: H
authors.lastname: Yokozaki
authors.forename: A
authors.initials: A
authors.lastname: Budillon
authors.forename: T
authors.initials: T
authors.lastname: Clair
authors.forename: K
authors.initials: K
authors.lastname: Kelley
authors.forename: K
authors.initials: K
authors.lastname: Cowan
authors.forename: C
authors.initials: C
authors.lastname: Rohlff
authors.forename: R
authors.initials: R
authors.lastname: Glazer
authors.forename: Y
authors.initials: Y
authors.lastname: Chochung