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

J. Balazsovits, Gordon Mills, J. Falk, R. Falk

Research output: Contribution to journalArticle

3 Citations (Scopus)

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
Externally publishedYes

Fingerprint

Mastocytoma
Cyclic AMP
Prostaglandins
Alprostadil
Calcium
Prostaglandin D2
Dinoprost
DNA
Chemical activation
Pertussis Toxin
Cell Surface Receptors
Type C Phospholipases
GTP-Binding Proteins
Adenylyl Cyclases
Thymidine
Fluorescence
Growth
prostaglandin B1

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology

Cite this

Prostaglandins inhibit proliferation of the murine P815 mastocytoma by decreasing cytoplasmic free calcium levels ([Ca+2]). / Balazsovits, J.; Mills, Gordon; Falk, J.; Falk, R.

In: Prostaglandins, Vol. 36, No. 2, 01.01.1988, p. 191-204.

Research output: Contribution to journalArticle

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