8-CHLOROADENOSINE 3',5'-MONOPHOSPHATE AS A NOVEL MODULATOR OF MULTIDRUG-RESISTANCE
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- Published online on: September 1, 1993 https://doi.org/10.3892/ijo.3.3.423
- Pages: 423-430
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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 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.
