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Different biological effects of the two protein kinase C activators bryostatin-1 and TPA on human carcinoma cell lines

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Abstract

Bryostatin 1 (Bryo) is a naturally occurring macrocyclic lactone with antineoplastic activity. Like the phorbol ester 12-O-tetradecanoyl-phorbol 13-acetate (TPA) it directly activates the calcium- and phospholipid-dependent protein kinase C (PKC), thus generating a number of different cellular responses. We investigated the effects of Bryo and TPA on DNA synthesis, proliferation, viability and c-myc protooncogene expression of the human carcinoma cell lines COLO-320, MEL-HO, and KB-3-1. TPA inhibited [3H]-thymidine incorporation in all three cell lines in a dose-dependent manner, whereas Bryo only inhibited the DNA synthesis in MEL-HO, but not in KB-3-1 and COLO-320 cells. Within the concentration ranges used, TPA and Bryo were found to have a low toxicity. Counting of the cells confirmed the observed inhibition of cell proliferation. However, the enzymatic conversion of MTT, applied as a colorimetric proliferation assay, was not significantly affected by both biomodulators.

Time-course experiments revealed a rapid onset of the inhibitory effect on DNA synthesis. Bryo was further able to antagonize the TPA-mediated effects on proliferation suggesting an (at least partially) different mode of action of these PKC activators. Incubation of MEL-HO and COLO-320 cells with either of the two biomodulators resulted in a rapid and strong increase of c-myc mRNA. The present study emphasizes Bryo as an interesting, natural substance for the study of PKC-mediated biological effects.

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Authors and Affiliations

  1. Department of Human and Animal Cell Cultures, DSM - German Collection of Microorganisms and Cell Cultures, Braunschweig, Germany

    Klaus G. Steube, Dörthe Grunicke & Hans G. Drexler

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  1. Klaus G. Steube
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  2. Dörthe Grunicke
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  3. Hans G. Drexler
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Steube, K.G., Grunicke, D. & Drexler, H.G. Different biological effects of the two protein kinase C activators bryostatin-1 and TPA on human carcinoma cell lines. Invest New Drugs 12, 15–23 (1994). https://doi.org/10.1007/BF00873230

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