Abstract |
The bryostatins, macrocyclic lactones isolated on the basis of their antineoplastic activity, activate protein kinase C in vitro and inhibit phorbol ester binding to the enzyme. In intact cells, the bryostatins induce some phorbol ester responses, such as neutrophil activation, but paradoxically they not only fail to induce other responses, e.g., differentiation in HL-60 promyelocytic leukemia cells, but actually block response to the phorbol esters. We compare here bryostatin I and phorbol 12,13-dibutyrate as inhibitors of cell-cell communication in cultured primary mouse epidermal cells. Like phorbol 12,13-dibutyrate, bryostatin I at nanomolar concentrations markedly inhibited cell coupling. It differed from the phorbol esters, however, in that its action was more transient. By 4 h of incubation bryostatin 1 caused little inhibition of coupling. Moreover, coincubation of bryostatin 1 and phorbol 12,13-dibutyrate gave no greater response at this time than that found for bryostatin 1 alone. Time-dependent inhibition of the protein kinase C pathway could account for many of the observed differences between the actions of the phorbol esters and bryostatin 1.
|
Authors | G Pasti, E Rivedal, S H Yuspa, C L Herald, G R Pettit, P M Blumberg |
Journal | Cancer research
(Cancer Res)
Vol. 48
Issue 2
Pg. 447-51
(Jan 15 1988)
ISSN: 0008-5472 [Print] United States |
PMID | 3422054
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
|
Chemical References |
- Bryostatins
- Lactones
- Macrolides
- Phorbol Esters
- Phorbol 12,13-Dibutyrate
- bryostatin 1
- Protein Kinase C
- Calcium
|
Topics |
- Animals
- Bryostatins
- Calcium
(physiology)
- Cell Communication
(drug effects)
- Cells, Cultured
- Dose-Response Relationship, Drug
- Lactones
(metabolism, pharmacology)
- Macrolides
- Mice
- Mice, Inbred BALB C
- Phorbol 12,13-Dibutyrate
- Phorbol Esters
(pharmacology)
- Protein Kinase C
(physiology)
- Skin
(drug effects)
- Time Factors
|