Bryostatin 1 induces prolonged activation of extracellular regulated protein kinases in and apoptosis of LNCaP human prostate cancer cells overexpressing protein kinase Cα Journal Article


Authors: Gschwend, J. E.; Fair, W. R.; Powell, C T.
Article Title: Bryostatin 1 induces prolonged activation of extracellular regulated protein kinases in and apoptosis of LNCaP human prostate cancer cells overexpressing protein kinase Cα
Abstract: Previously, we reported that 12-O-tetradecanoylphorbol-13-acetate (TPA)- induced apoptosis of LNCaP human prostate cancer cells was accompanied by prolonged translocation of protein kinase C (PKC)α to non-nuclear membranes and that TPA-resistant LNCaP cells had down-regulated PKCα. Here we show that 10 nM bryostatin 1 induced transient membrane translocation and down- regulation of PKCα, prolonged translocation of PKCδ and ε to non-nuclear membranes, and did not induce cell death but blocked TPA-induced apoptosis. To test the hypothesis that inhibition of TPA-induced apoptosis by bryostatin 1 was due to down-regulation of PKCα, we inducibly overexpressed PKCα in LNCaP cells. Overexpression of PKCα alone did not induce apoptosis, even in clones that contained much more membrane-bound, active PKCα than was observed in TPA-treated untransfected LNCaP cells. However, the addition of 10 nM bryostatin 1 to PKCα-overexpressing LNCaP cells did not yield down- regulation of PKCα and induced extensive apoptosis. Immunoblot analysis revealed that TPA induced prolonged hyperphosphorylation of Raf-1 and activation of extracellular-regulated/mitogen-activated protein kinases 1 and 2 in untransfected LNCaP cells, as did bryostatin 1 in PKCα-overexpressing cells. On the other hand, bryostatin 1 induced only transient hyperphosphorylation of Raf-1 and activation of extracellular- regulated/mitogen-activated protein kinases 1 and 2 in untransfected LNCaP cells. These results confirm a role of prolonged membrane-associated PKCα in PKC activator-mediated LNCaP apoptosis and suggest involvement of the mitogen-activated protein kinase pathway.
Keywords: mitogen activated protein kinase; controlled study; human cell; antineoplastic agents; cell division; gene overexpression; apoptosis; cell growth; down-regulation; cancer cell culture; enzyme activation; tumor cells, cultured; phosphorylation; prostate cancer; prostatic neoplasms; immunoblotting; protein kinase c; down regulation; mitogen-activated protein kinases; bryostatin 1; subcellular fractions; biological transport; isoenzymes; phorbol 13 acetate 12 myristate; protein kinase c-alpha; tetradecanoylphorbol acetate; carcinogens; lactones; proto-oncogene proteins c-raf; isoenzyme; macrolides; humans; human; male; priority journal; article
Journal Title: Molecular Pharmacology
Volume: 57
Issue: 6
ISSN: 0026-895X
Publisher: The American Society for Pharmacology and Experimental Therapeutics  
Date Published: 2000-06-01
Start Page: 1224
End Page: 1234
Language: English
PUBMED: 10825394
PROVIDER: scopus
DOI/URL:
Notes: Export Date: 18 November 2015 -- Source: Scopus