Successful treatment of murine melanoma with bryostatin

Lynn M. Schlichter, Ahmed H. Esa, W. Stratford May, Mary K. Laulis, George Pettit, Allan D. Hess

Research output: Contribution to journalArticle

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Abstract

Bryostatins are a novel class of protein kinase C activators which were isolated from the marine bryozoan Bugula neritina and found to possess both antineoplastic and immunoenhancing properties. In this report, we examined the relationship between the in vivo and in vitro antineoplastic effects of bryostatin 1. The in vivo antitumor activity of bryostatin 1 was demonstrated in a B16 melanoma pulmonary metastases model, in which treatment of tumor-bearing C57BL/6 mice with 5 days of bryostatin I resulted in a significant reduction in the number of lung nodules (control, 87; bryostatin, 7). There was a clear dose-response effect, with the optimal antimelanoma dose being 100 μg/kg/day, but even low doses of bryostatin 1 of 1 μg/kg/day resulted in a 53% reduction in the number of metastases. Although bryostatin 1 shares many biological properties with the phorbol esters, parallel treatment with 12-O-tetradecanoyl 13-phorbol acetate was ineffective against B16 melanoma in vivo. Using a clonogenic assay, bryostatin 1 was found to have a direct antiproliferative effect against B16 melanoma. This inhibition occurred at relatively high bryostatin 1 concentrations (10-6 M), in comparison with a sensitive cell line REH (10-10 M). Treatment of mice with bryostatin 1 or preincubation of normal spleen cells with bryostatin 1 failed to enhance nonspecific cell-mediated cytotoxicity against B16 melanoma in vitro. Moreover, bryostatin 1 was found to inhibit both natural killer cell activity and interleukin 2 generation of lymphokine-activated killer cells. Thus, a role for an in vivo immune enhancement mechanism as the basis for the antimelanoma activity observed with bryostatin 1 cannot be invoked from these experiments. These findings indicate that bryostatin 1 may act directly on the B16 melanoma pulmonary metastases. The precise mechanism whereby bryostatin exerts its antimelanoma effects remains unclear.

Original languageEnglish (US)
Pages (from-to)682-687
Number of pages6
JournalCancer Research
Volume51
Issue number2
StatePublished - Jan 15 1991
Externally publishedYes

Fingerprint

Bryostatins
Melanoma
Experimental Melanomas
Neoplasm Metastasis
Antineoplastic Agents
Lung
bryostatin 1
Lymphokine-Activated Killer Cells
Phorbol Esters
Tetradecanoylphorbol Acetate
Inbred C57BL Mouse
Natural Killer Cells
Protein Kinase C
Interleukin-2

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Schlichter, L. M., Esa, A. H., Stratford May, W., Laulis, M. K., Pettit, G., & Hess, A. D. (1991). Successful treatment of murine melanoma with bryostatin. Cancer Research, 51(2), 682-687.

Successful treatment of murine melanoma with bryostatin. / Schlichter, Lynn M.; Esa, Ahmed H.; Stratford May, W.; Laulis, Mary K.; Pettit, George; Hess, Allan D.

In: Cancer Research, Vol. 51, No. 2, 15.01.1991, p. 682-687.

Research output: Contribution to journalArticle

Schlichter, LM, Esa, AH, Stratford May, W, Laulis, MK, Pettit, G & Hess, AD 1991, 'Successful treatment of murine melanoma with bryostatin', Cancer Research, vol. 51, no. 2, pp. 682-687.
Schlichter LM, Esa AH, Stratford May W, Laulis MK, Pettit G, Hess AD. Successful treatment of murine melanoma with bryostatin. Cancer Research. 1991 Jan 15;51(2):682-687.
Schlichter, Lynn M. ; Esa, Ahmed H. ; Stratford May, W. ; Laulis, Mary K. ; Pettit, George ; Hess, Allan D. / Successful treatment of murine melanoma with bryostatin. In: Cancer Research. 1991 ; Vol. 51, No. 2. pp. 682-687.
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