Bryostatin-1: Pharmacology and therapeutic potential as a CNS drug

CNS Drug Reviews

Volumn 12, Issue 1, 2006, Pages 1-8

  Sun, Miao Kun ^a   Alkon, Daniel L ^a  

^a Blanchette Rockefeller Neurosciences Institute   (United States)

Author keywords

Alzheimer's disease; Antidepressants; Bryostatin 1; Cognition activation; Depression; Learning and memory; Mood; Protein kinase C

Indexed keywords

ANTIDEPRESSANT AGENT; BRYOSTATIN 1; ISOENZYME; PROTEIN KINASE C ACTIVATOR; TAU PROTEIN;

ANOREXIA; CENTRAL NERVOUS SYSTEM; COGNITION; DRUG ACTIVATION; DRUG DISTRIBUTION; DRUG DOSE REGIMEN; DRUG HALF LIFE; DRUG INHIBITION; DRUG MECHANISM; DRUG TARGETING; FATIGUE; FEVER; HEADACHE; HUMAN; LETHARGY; LEUKOPENIA; LIVER DYSFUNCTION; LONG TERM MEMORY; MYALGIA; NAUSEA; NONHUMAN; ODYNOPHAGIA; PHOTOPHOBIA; PROTEIN PHOSPHORYLATION; PROTEIN SYNTHESIS; REVIEW; THROMBOCYTOPENIA; TUMOR GROWTH;

ALZHEIMER DISEASE; ANIMALS; ANTINEOPLASTIC AGENTS; CENTRAL NERVOUS SYSTEM; DEPRESSION; ENZYME ACTIVATION; HUMANS; MACROLIDES; PROTEIN KINASE C;

EID: 33746555648     PISSN: 1080563X     EISSN: None     Source Type: Journal    
DOI: 10.1111/j.1527-3458.2006.00001.x     Document Type: Review

References (50)

1. Akin D, Hal Manier D, Sanders-Bush E, Shelton RC. Signal transduclion abnormalities in melancholic depression. Int J Neuropsychopharmacol 2005;8:5-16.
2. Ali S, Aranha O, Li YW, Pettit GR, Sarkar FH, Philip PA. Sensitization of human breast cancer cells to gemcitabine by the protein kinase C modulator bryostatin-1. Cancer Chemother Pharm 2003;52:235-246.
3. Al-Katib AM, Smith MR, Kamanda WS, et al. Bryostatin-1 down-regulates mdr1 and potentiates vincristine cytotoxicity in diffuse large cell lymphoma xenografts. Clin Cancer Res. 1998;4:1305-1314.
4. + channel cascade. Trends Neurosci 1998;21:529-537.
5. Alkon DL, Epstein H, Kuzirian A, Bennett M. C, Nelson TJ. Protein synthesis required for long-term memory is induced by PKC activation on days before associative learning. Proc Natl Acad Sci USA 2005;102:16432-16437.
6. Bank B, DeWeer A, Kuzirian AM, Rasmussen H, Alkon DL. Classical conditioning induces long-term translocation of protein kinase C in rabbit hippocampal CA1 cells. Proc Natl Acad Sci USA 1988;85:1988-1992.
7. Cho JH, Johnson GV. Glycogen synthase kinase 3 beta induces caspase-cleaved tau aggregation in situ. J Biol Chem 2004;279:54716-54723.
8. Clamp A, Jayson GC. The clinical development of the bryostatins. Anti-Cancer Drugs 2002;13:673-683.
9. Clamp AR, Blackhall FH, Vasey P, et al. A phase II trial of bryostatin-1 administered by weekly 24-hour infusion in recurrent epithelial ovarian carcinoma. Br. J Cancer 2003;89:1152-1154.
10. Cole G, Dobkins KR, Hansen LA, Terry RD, Saitoh T. Decreased levels of protein kinase C in Alzheimer brain. Brain Res 1988;452:165-174.
11. Curiel RE, Garcia CS, Farooq L, Aguero MF, Espinoza-Dagado I. Bryostatin-1 and IL-2 synergize to induce IFN-gamma expression in human peripheral blood T cells: Implications for cancer immunotherapy. J Immunol 2001;167:4828-4837.
12. de Vries D, Herald CL, Pettit HG, Blumberg PM. Demonstration of sub-nanomolar affinity of bryostatin-1 for the phorbol ester receptor in rat brain. Biochem Pharmacol 1988;37:4069-4073.
13. Dowlati A, Lazarus HM, Hartman P, et al. Phase I and correlative study of combination bryostatin-1 and vincristine in relapsed B-cell malignancies. Clin Cancer Res 2003;9:5929-5935.
14. Etcheberrigaray R, Tan M, Dewachter I, et al. Therapeutic effects of PKC activators in Alzheimer's disease transgenic mice. Proc Natl Acad Sci USA 2004;101:11141-11146.
15. Fang X, Yu S, Tanyi JL, Lu Y, Woodgett JR, Mills GB. Convergence of multiple signaling cascades at glycogen synthase kinase 3: Edg receptor-mediated phsophorylation and inactivation by lysophosphatidic acid through a protein kinase C-dependent intracellular pathway. Mol Cell Biol 2002;22:2099-2110.
16. Favit A, Grimaldi M, Nelson TJ, Alkon DL. Alzheimer's-specific effects of soluble β-amyloid on protein kinase C-α and -γ degradation in human fibroblasts. Proc Natl Acad Sci USA 1998;10:5562-5567.
17. Hennings H, Blumberg PM, Pettit GR, Herald CL, Shores R, Yuspa SH. Bryostatin-1, an activator of protein kinase C, inhibits tumor promotion by phorbol esters in SENCAR mouse skin. Carcinogenesis 1987;8:1343-1346.
18. 31P magnetic resonance spectroscopic study. Br J Cancer 1995;72:998-1003.
19. Hofmann J Protein kinase C isozymes as potential targets for anticancer therapy. Curr Cancer Drug Targets 2004;4:125-146.
20. Jayson GC, Crowther D, Prendiville J, et al. A phase I trial of bryostatin-1 in patients with advanced malignancy using a 24 hour intravenous infusion. Br J Cancer 1995;72:461-468.
21. Kinouchi T, Sorimachi H, Maruyama K, et al. Conventional protein kinase C (PKC)-alpha and novel PKC epsilon, but not-delta, increase the secretion of an N-terminal fragment of Alzheimer's disease amyloid precursor protein from PKC cDNA transfected 3Y1 fibroblasts. FEBS Lett 1995;364:203-206.
22. Kraft AS, Reeves JA, Ashendel CL. Differing modulation of protein kinase C by bryostatin-1 and phorbol esters in JB6 mouse epidermal cells. J Biol Chem 1988;263:8437.
23. Lavoie L, Band CJ, Kong M, Bergeron JJM, Posner BI. Regulation of glycogen synthase in rat hepatocytes. Evidence for multiple signaling pathway. J Biol Chem 1999;274:28279-28285.
24. Lee W, Boo JH, Jung MW, et al. Amyloid beta peptide directly inhibits PKC activation. Mol Cell Neurosci 2004;26:222-231.
25. Matthews SA, Pettit GR, Rozengurt E. Bryostatin-1 induces biphasic activation of protein kinase D in intact cells. J Biol Chem 1997;272:20245- 20250.
26. Mutter R, Wills M. Chemistry and clinical biology of the bryostatins. Bioorg Med Chem 2000;8:1841-1860.
27. Nezhat F, Wadler S, Muggia F, et al. Phase II trial of the combination of bryostatin-1 and cisplatin in advanced or recurrent carcinoma of the cervix: A New York Gynecologic Oncology Group Study. Gynecol Oncol 2004;93:144-148.
28. Pacheco MA, Stockmeier C, Meltzer NY, Overholser JC, Dilley GE, Jope RS. Alterations in phosphoinositide signaling and G-protein levels in depressed suicide brain. Brain Res 1996;723:37-45.
29. Pákáski M, Bjelik A, Hugyecz M, Kása P, Janka Z, Kalman J. Imipramine and citalopram facilitate amyloid precursor protein secretion in vitro. Neurochem Intern 2005;47:190-195.
30. Pandey GN, Dwivedi Y. Effects of adrenal glucocorticoid on protein kinase C (PKC) binding sites, PKC activity and expression of PKC isozymes in the brain. J Neurochem 2000;74:S21D.
31. Pandey GN, Dwivedi Y, Ren X, et al. Altered expression and phosphorylation of myristoylated alanine-rich C kinase (MARCKS) in postmortem brain of suicide victims with or without depression. J Psychiatr Res 2003;37:421-432.
32. Pandey GN, Ewivedi Y, Rizavi HS, Ren X, Conley RR. Decreased catalytic activity and expression of protein kinase C isozymes in teenage suicide victims. Arch Gen Psychiatry 2004;61:685-693.
33. Pettit GR, Herald CL, Doubek DL, Arnold E, Clardy J. Isolation and structures of bryostatin-1. J Am Chem Soc 1982;104:6846-6848.
34. Pascale A, Amadio M, Scapagnini G, et al. Neuronal ELAV proteins enhances mRNA stability by a PKCα-dependent pathway. Proc Natl Acad Sci USA 2005;102:12065-12070.
35. Rahimian R, Hrdina PD. Possible role of protein kinase C in regulation of 5-hydroxytryptamine 2A receptors in rat brain. Can J Physiol Pharmacol 1995;73:1686-1691.
36. Ramamoorthy S, Giovanetti E, Qian Y, Blakely RD. Phosphorylation and regulation of antidepressant-sensitive serotonin transporters. J Biol Chem 1998;273:2458-2466.
37. Spitaler M, Utz I, Hilbe W, Hofmann J, Grunicke HH. PKC-independent modulation of multidrug resistance in cells with mutant (V185) but not wild-type (G185) P-glycoprotein by bryostatin-1. Biochem Pharm 1998;56:861-869.
38. Sun M-K, Alkon DL. Depressed or demented: Common CNS drug targets?! Curr Drug Targets. CNS Neurol Disord 2002;1:573-589.
39. Sun M-K, Alkon DL. Dual effects of bryostatin-1 on spatial memory and depression. Eur J Pharmacol 2005;512:43-51.
40. Sun M-K, Alkon DL. Protein kinase C isozymes: Memory therapeutic potential. Curr Drug Targets. CNS Neurol Disord 2005;4:541-52.
41. Szallasi Z, Du L, Levine R, et al. The bryostatins inhibit growth of B16/F10 melanoma cells in vitro through a protein kinase C-independent mechanism: Dissociation of activities using 26-epi-bryostatin-1. Cancer Res 1996;56:2105-2111.
42. Weeber EJ, Atkins CM, Selcher JC, et al. A role for the b isoform of protein kinase C in fear conditioning. J Neurosci 2000;20:5906-5914.
43. Weitman S, Langevin AM, Berkow RL, et al. A phase I trial of bryostatin-1 in children with refractory solid tumors: A pediatric oncology group study. Clin Cancer Res 1999;5:2344-2348.
44. Wender PA, Baryza JL, Bennett CE, et al. The practical synthesis of a novel and highly potent analogue of bryostatin. J Am Chem Soc 2002;124:13648-13649.
45. Wender PA, Baryza JL. Identification of a tunable site in bryostatin analogs: C20 bryologs through late stage diversification. Org Lett 2005;7:1177-1180.
46. Wender PA, Clarke MO, Horan JC. Role of the A-ring of bryostatin analogues in PKC binding: Synthesis and initial biological evaluation of new A-ring-modified bryologs. Org Lett 2005;7:1995-1998.
47. Yeon SW, Jung MW, Ha MJ, et al. Blockade of PKC epsilon activation attenuates phorbol ester-induced increase of alpha-secretase-derived secreted form of amyloid precursor protein. Biochem Biophys Res Commun 2001;280:782-787.
48. Zhang X, Zhang R, Zhao H, et al. Preclinical pharmacology of the natural product anticancer agent bryostatin-1, an activator of protein kinase C. Cancer Res 56:802-808, 1996.
49. Zhao M, Rudek MA, He P, Smith, BD, Baker S.D. Validation and implementation of a method for determination of bryostatin-1 in human plasma by using liquid chromatography/tandem mass spectrometry. Ann Biochem 337:143-148, 2005.
50. Zhu G, Wang D, Lin YH, McMahon T, Koo EH, Messing RO. Protein kinase C epsilon suppresses Abeta production and promotes activation of α-secretase. Biochem Biophys Res Commun 2001;285:997-1006.