Skip to main content
British Journal of Cancer logoLink to British Journal of Cancer
. 1998;77(2):216–220. doi: 10.1038/bjc.1998.36

Bryostatin 1-tamoxifen combinations show synergistic effects on the inhibition of growth of P388 cells in vitro.

A T McGown 1, G Jayson 1, G R Pettit 1, M S Haran 1, T H Ward 1, D Crowther 1
PMCID: PMC2151232  PMID: 9460991

Abstract

This study shows that combinations of bryostatin 1, a novel modulator of protein kinase C currently under clinical evaluation, with the anti-oestrogenic agent tamoxifen caused a large synergistic enhancement of growth inhibition in P388 cells in vitro. The growth-inhibitory effects of bryostatin 1 in the presence of non-inhibitory concentrations of tamoxifen were increased by approximately 200-fold, whereas growth inhibition by tamoxifen in the presence of non-inhibitory concentrations of bryostatin 1 were increased over 30-fold. These data have been confirmed by isobologram analysis. The precise mechanism underlying this effect is unknown, although preliminary data implicating protein kinase C is presented. The magnitude of this synergistic effect, together with evidence of clinical responses seen when these agents were given sequentially in ovarian cancer, merits further study.

Full text

PDF
216

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Ahlgren J. D., Ellison N. M., Gottlieb R. J., Laluna F., Lokich J. J., Sinclair P. R., Ueno W., Wampler G. L., Yeung K. Y., Alt D. Hormonal palliation of chemoresistant ovarian cancer: three consecutive phase II trials of the Mid-Atlantic Oncology Program. J Clin Oncol. 1993 Oct;11(10):1957–1968. doi: 10.1200/JCO.1993.11.10.1957. [DOI] [PubMed] [Google Scholar]
  2. Azzi A., Boscoboinik D., Hensey C. The protein kinase C family. Eur J Biochem. 1992 Sep 15;208(3):547–557. doi: 10.1111/j.1432-1033.1992.tb17219.x. [DOI] [PubMed] [Google Scholar]
  3. Berkow R. L., Kraft A. S. Bryostatin, a non-phorbol macrocyclic lactone, activates intact human polymorphonuclear leukocytes and binds to the phorbol ester receptor. Biochem Biophys Res Commun. 1985 Sep 30;131(3):1109–1116. doi: 10.1016/0006-291x(85)90205-0. [DOI] [PubMed] [Google Scholar]
  4. Dale I. L., Gescher A. Effects of activators of protein kinase C, including bryostatins 1 and 2, on the growth of A549 human lung carcinoma cells. Int J Cancer. 1989 Jan 15;43(1):158–163. doi: 10.1002/ijc.2910430129. [DOI] [PubMed] [Google Scholar]
  5. Gescher A. Towards selective pharmacological modulation of protein kinase C--opportunities for the development of novel antineoplastic agents. Br J Cancer. 1992 Jul;66(1):10–19. doi: 10.1038/bjc.1992.209. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Hennings H., Blumberg P. M., Pettit G. R., Herald C. L., Shores R., Yuspa S. H. Bryostatin 1, an activator of protein kinase C, inhibits tumor promotion by phorbol esters in SENCAR mouse skin. Carcinogenesis. 1987 Sep;8(9):1343–1346. doi: 10.1093/carcin/8.9.1343. [DOI] [PubMed] [Google Scholar]
  7. Hocevar B. A., Morrow D. M., Tykocinski M. L., Fields A. P. Protein kinase C isotypes in human erythroleukemia cell proliferation and differentiation. J Cell Sci. 1992 Mar;101(Pt 3):671–679. doi: 10.1242/jcs.101.3.671. [DOI] [PubMed] [Google Scholar]
  8. Hornung R. L., Pearson J. W., Beckwith M., Longo D. L. Preclinical evaluation of bryostatin as an anticancer agent against several murine tumor cell lines: in vitro versus in vivo activity. Cancer Res. 1992 Jan 1;52(1):101–107. [PubMed] [Google Scholar]
  9. Jayson G. C., Crowther D., Prendiville J., McGown A. T., Scheid C., Stern P., Young R., Brenchley P., Chang J., Owens S. A phase I trial of bryostatin 1 in patients with advanced malignancy using a 24 hour intravenous infusion. Br J Cancer. 1995 Aug;72(2):461–468. doi: 10.1038/bjc.1995.356. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Jetten A. M., George M. A., Pettit G. R., Rearick J. I. Effects of bryostatins and retinoic acid on phorbol ester- and diacylglycerol-induced squamous differentiation in human tracheobronchial epithelial cells. Cancer Res. 1989 Jul 15;49(14):3990–3995. [PubMed] [Google Scholar]
  11. Kennedy M. J., Prestigiacomo L. J., Tyler G., May W. S., Davidson N. E. Differential effects of bryostatin 1 and phorbol ester on human breast cancer cell lines. Cancer Res. 1992 Mar 1;52(5):1278–1283. [PubMed] [Google Scholar]
  12. Levine B. L., May W. S., Tyler P. G., Hess A. D. Response of Jurkat T cells to phorbol ester and bryostatin. Development of sublines with distinct functional responses and changes in protein kinase C activity. J Immunol. 1991 Nov 15;147(10):3474–3481. [PubMed] [Google Scholar]
  13. O'Brian C. A., Housey G. M., Weinstein I. B. Specific and direct binding of protein kinase C to an immobilized tamoxifen analogue. Cancer Res. 1988 Jul 1;48(13):3626–3629. [PubMed] [Google Scholar]
  14. Philip P. A., Rea D., Thavasu P., Carmichael J., Stuart N. S., Rockett H., Talbot D. C., Ganesan T., Pettit G. R., Balkwill F. Phase I study of bryostatin 1: assessment of interleukin 6 and tumor necrosis factor alpha induction in vivo. The Cancer Research Campaign Phase I Committee. J Natl Cancer Inst. 1993 Nov 17;85(22):1812–1818. doi: 10.1093/jnci/85.22.1812. [DOI] [PubMed] [Google Scholar]
  15. Prendiville J., Crowther D., Thatcher N., Woll P. J., Fox B. W., McGown A., Testa N., Stern P., McDermott R., Potter M. A phase I study of intravenous bryostatin 1 in patients with advanced cancer. Br J Cancer. 1993 Aug;68(2):418–424. doi: 10.1038/bjc.1993.352. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Prendiville J., McGown A. T., Gescher A., Dickson A. J., Courage C., Pettit G. R., Crowther D., Fox B. W. Establishment of a murine leukaemia cell line resistant to the growth-inhibitory effect of bryostatin 1. Br J Cancer. 1994 Oct;70(4):573–578. doi: 10.1038/bjc.1994.353. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Steel G. G., Peckham M. J. Exploitable mechanisms in combined radiotherapy-chemotherapy: the concept of additivity. Int J Radiat Oncol Biol Phys. 1979 Jan;5(1):85–91. doi: 10.1016/0360-3016(79)90044-0. [DOI] [PubMed] [Google Scholar]
  18. Vistica D. T., Skehan P., Scudiero D., Monks A., Pittman A., Boyd M. R. Tetrazolium-based assays for cellular viability: a critical examination of selected parameters affecting formazan production. Cancer Res. 1991 May 15;51(10):2515–2520. [PubMed] [Google Scholar]
  19. Yasuda I., Kishimoto A., Tanaka S., Tominaga M., Sakurai A., Nishizuka Y. A synthetic peptide substrate for selective assay of protein kinase C. Biochem Biophys Res Commun. 1990 Feb 14;166(3):1220–1227. doi: 10.1016/0006-291x(90)90996-z. [DOI] [PubMed] [Google Scholar]

Articles from British Journal of Cancer are provided here courtesy of Cancer Research UK

RESOURCES