Prostaglandins inhibit proliferation of the murine P815 mastocytoma by decreasing cytoplasmic free calcium levels ([Ca+2])

J. Balazsovits, G. Mills, J. Falk, R. Falk

    Research output: Contribution to journalArticle

    3 Scopus citations

    Abstract

    Prostaglandins inhibit the proliferation of the murine P815 mastocytoma. The mechanism of this antitumour activity remains underfined. In several cell systems, the action of PGs is inhibited at the cell surface receptor by pertussis toxin likely through regulatory G proteins involved in the inhibition of adenyl cyclase or activation of phospholipase C. We therefore determined the effect of prostaglandins on the biochemical consequences of activation of these pathways; i.e. concentrations of cyclic AMP (cAMP) and cytosolic free Ca+2 concentrations ([Ca+2]i) respectively. PGD2 (6 ug/mL), PGE1 (10 ug/mL) and PGB1 (50 ug/mL) maximally inhibited (3H)- thymidine incorporation to DNA. PGF2 alpha did not affect DNA synthesis. PGE1 (10 ug/mL) induced a three fold increase in cAMP concentrations. In contrast, the other prostaglandins did not alter cAMP concentrations. Maximal growth inhibitory doses of PGD2, PGE1 and PGB1 decrease [Ca+2]i, as measured by the fluorescence of Indo-1, from 320 +/- 5 nM to 172 +/- 20 nM, 161 +/- 12 nM, and 151 +/- 18 nM respectively. PGF2 alpha did not alter [Ca+2]i. Therefore, in contrast to the effects on cAMP, the decrease in [Ca+2]i was concordant with the inhibition of DNA synthesis. This suggests that PGs may inhibit proliferation through decreasing [Ca+2] in the P815 mastocytoma.

    Original languageEnglish (US)
    Pages (from-to)191-204
    Number of pages14
    JournalProstaglandins
    Volume36
    Issue number2
    DOIs
    StatePublished - Jan 1 1988

    ASJC Scopus subject areas

    • Biochemistry
    • Endocrinology

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