dinoprost and Mast-Cell-Sarcoma

P-815 mouse mastocytoma cells express the K isozyme of pyruvate kinase and the specific activity of this enzyme is increased in response to N6,2'-O-dibutyryladenosine 3':5'-cyclic monophosphate, 8-bromoadenosine 3':5'-cyclic monophosphate, cholera toxin, and epinephrine, all of which also elevate the intracellular concentration of adenosine 3':5'-cyclic monophosphate. Prostaglandin F2 alpha also increases the cellular activity of this enzyme, but does not increase the adenosine 3':5'-cyclic monophosphate levels. Under all these conditions, the increase in enzymatic activity is accompanied by an equivalent increase in the pyruvate kinase protein level. However, neither the rate of enzyme synthesis nor the level of pyruvate kinase mRNA is elevated by N6,2'-O-dibutyryladenosine 3':5'-cyclic monophosphate. On the other hand, it does increase the enzyme's half-life. In contrast, prostaglandin F2 alpha increases the rate of synthesis and the level of pyruvate kinase K mRNA, but has no influence on the rate of degradation. Therefore, these cells have two mechanisms which increase pyruvate kinase K levels. One operates via an increase in cAMP level and results in a decrease in the rate of degradation, whereas the other minimizes an upsurge in cAMP levels but still increases pyruvate kinase K activity by increasing its rate of synthesis.

Topics: 8-Bromo Cyclic Adenosine Monophosphate; Animals; Bucladesine; Cell Line; Cholera Toxin; Cyclic AMP; Dinoprost; Epinephrine; Isoenzymes; Kinetics; Mast-Cell Sarcoma; Mice; Pyruvate Kinase

P-815 mastocytoma cells increase the level of pyruvate kinase (PK) expression in response to chloroform-methanol extracts of conditioned media, butyrate, and dibutyryl cyclic AMP (but2cAMP) plus theophylline. The butyrate effect is indomethacin sensitive, suggesting a prostaglandin (PG) is the active signaling factor. Moreover, the chloroform-methanol extracts contain PGE2 and PGF2 alpha and additions of the latter enhance PK activity. PGE2 alone has little or no effect but acts synergistically with PGF2 alpha. These data show that PGF2 alpha can regulate PK levels. On the other hand, other factors may also be active, since the endogeneous and the but2cAMP plus theophylline effects are indomethacin insensitive. Most of the factors that increase PK activity also inhibit cellular growth; however, regulation of PK expression can be uncoupled from growth inhibition.

Topics: Animals; Bucladesine; Butyrates; Butyric Acid; Dinoprost; Dinoprostone; Drug Synergism; Indomethacin; Mast-Cell Sarcoma; Mice; Prostaglandins; Prostaglandins E; Prostaglandins F; Pyruvate Kinase; Theophylline

The effects of prostaglandins D2, E2 and F2 alpha on the growth of murine mastocytoma cells were investigated by adding them to cultures at concentrations of 0.1 - 50 micrograms/ml. At the same time, their effects on DNA synthesis were investigated. Of these prostaglandins, prostaglandin D2 was the strongest inhibitor of mastocytoma cell growth and at 10 micrograms/ml of medium it also caused cell death within 24 h. Prostaglandin E2 at this concentration only inhibited cell growth. Prostaglandin F2 alpha had no effect on cell growth at concentrations of up to 50 micrograms/ml. These findings show that prostaglandin D2 is a strong anti-proliferative agent.

Topics: Animals; Cell Division; Cell Line; Cell Survival; Dinoprost; Dinoprostone; DNA Replication; DNA, Neoplasm; Female; Mast-Cell Sarcoma; Mice; Prostaglandin D2; Prostaglandins D; Prostaglandins E; Prostaglandins F