{Beta}2-adrenergic receptor agonists inhibit the proliferation of 1321N1 astrocytoma cells.

ABSTRACT: Astrocytomas and glioblastomas have been particularly difficult to treat and refractory to chemotherapy. However, significant evidence has been presented that demonstrates a decrease in astrocytoma cell proliferation subsequent to an increase in cAMP levels. The 1321N1 astrocytoma cell line, as well as other astrocytomas and glioblastomas, expresses ?(2)-adrenergic receptors (?(2)-ARs) that are coupled to G(s) activation and consequent cAMP production. Experiments were conducted to determine whether the ?(2)-AR agonist (R,R')-fenoterol and other ?(2)-AR agonists could attenuate mitogenesis and, if so, by what mechanism. Receptor binding studies were conducted to characterize ?(2)-AR found in 1321N1 and U118 cell membranes. In addition, cells were incubated with (R,R')-fenoterol and analogs to determine their ability to stimulate intracellular cAMP accumulation and inhibit [(3)H]thymidine incorporation into the cells. 1321N1 cells contain significant levels of ?(2)-AR as determined by receptor binding. (R,R')-fenoterol and other ?(2)-AR agonists, as well as forskolin, stimulated cAMP accumulation in a dose-dependent manner. Accumulation of cAMP induced a decrease in [(3)H]thymidine incorporation. There was a correlation between concentration required to stimulate cAMP accumulation and inhibit [(3)H]thymidine incorporation. U118 cells have a reduced number of ?(2)-ARs and a concomitant reduction in the ability of ?(2)-AR agonists to inhibit cell proliferation. These studies demonstrate the efficacy of ?(2)-AR agonists for inhibition of growth of the astrocytoma cell lines. Because a significant portion of brain tumors contain ?(2)-ARs to a greater extent than whole brain, (R,R')-fenoterol, or some analog, may be useful in the treatment of brain tumors after biopsy to determine ?(2)-AR expression.

SUBMITTER: Toll L 

PROVIDER: S-EPMC3033720 | biostudies-literature | 2011 Feb

REPOSITORIES: biostudies-literature