Bryostatins: potent, new activators of protein kinase C
Bryostatins (B) are a class of 17 macrocyclic lactones that have antineoplastic activity in the murine P388 lymphocytic leukemia system. Bryostatin-1 (B-1) is a potent co-mitogen for the Swiss 3T3 line of murine fibroblasts that have been arrested in G/sub 1//G/sub 0/. B-1 and insulin synergistically increase entry into the S phase of the cell cycle measured autoradiographically as % nuclei labeled with (/sup 3/H)thymidine. A prior treatment of the cells with phorbol 13-myristate 12-acetate (PMA) selectively eliminated the mitogenic response to B-1 or PMA. Conversely, a prior treatment of the cells with B-1 eliminated the mitogenic response to PMA or B-1. Five other B are approximately equipotent to B-1, but B-3 is 5 to 10 times less potent than B-1 as a mitogen. B-1 inhibits the binding of (/sup 3/H)phorbol dibutyrate ((/sup 3/H)PDB) at 4/sup 0/C to a high affinity receptor in the cells. B-3 was also less potent than B-1 as an inhibitor of (/sup 3/H)PDB binding. B-3 differs from B-1 in the diacylglycerol-like component of the molecule. In vitro B-1 and PMA are similarly potent activators of protein kinase C from bovine brain. Further comparisons of the relative activities of the various B are needed to define the structural features that are critical for the activation of protein kinase C which may help in the design of tumor promoter antagonists.
- Research Organization:
- Univ. of Alabama, Birmingham
- OSTI ID:
- 5447601
- Report Number(s):
- CONF-8604222-
- Journal Information:
- Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States), Vol. 45:3; Conference: 70. annual meeting of the Federation of American Society for Experimental Biology, St. Louis, MO, USA, 13 Apr 1986
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
59 BASIC BIOLOGICAL SCIENCES
LACTONES
BIOLOGICAL EFFECTS
PHORBOL ESTERS
CARCINOGENESIS
PHOSPHOTRANSFERASES
ENZYME ACTIVITY
AUTORADIOGRAPHY
BRAIN
CATTLE
CELL NUCLEI
FIBROBLASTS
INSULIN
LEUKEMIA
LYMPHOCYTES
MICE
THYMIDINE
TRITIUM COMPOUNDS
ANIMAL CELLS
ANIMALS
AZINES
BIOLOGICAL MATERIALS
BLOOD
BLOOD CELLS
BODY
BODY FLUIDS
CARCINOGENS
CELL CONSTITUENTS
CENTRAL NERVOUS SYSTEM
CONNECTIVE TISSUE CELLS
DISEASES
DOMESTIC ANIMALS
ENZYMES
ESTERS
HEMIC DISEASES
HETEROCYCLIC COMPOUNDS
HORMONES
LABELLED COMPOUNDS
LEUKOCYTES
MAMMALS
MATERIALS
NEOPLASMS
NERVOUS SYSTEM
NUCLEOSIDES
NUCLEOTIDES
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANS
PATHOGENESIS
PEPTIDE HORMONES
PHOSPHORUS-GROUP TRANSFERASES
PYRIMIDINES
RIBOSIDES
RODENTS
RUMINANTS
SOMATIC CELLS
TRANSFERASES
VERTEBRATES
560301* - Chemicals Metabolism & Toxicology- Cells- (-1987)
550901 - Pathology- Tracer Techniques