Different biological effects of the two protein kinase C activators bryostatin-1 and TPA on human carcinoma cell lines.
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.
DSM-German Collection of Microorganisms and Cell Cultures, Department of Human and Animal Cell Cultures, Braunschweig, Germany.
K G
KG
Steube
D
D
Grunicke
H G
HG
Drexler
D000230:Adenocarcinoma / Q000473:pathology; D000970:Antineoplastic Agents / Q000494:pharmacology*; D054713:Bryostatins; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004247:DNA / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D016259:Genes, myc / Q000187:drug effects; D006801:Humans; D007783:Lactones / Q000494:pharmacology*; D018942:Macrolides; D008545:Melanoma / Q000473:pathology; D011493:Protein Kinase C / Q000378:metabolism; D016271:Proto-Oncogene Proteins c-myc / Q000187:drug effects* / Q000235:genetics; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D012811:Sigmoid Neoplasms / Q000473:pathology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D002583:Uterine Cervical Neoplasms / Q000473:pathology
D000970:Antineoplastic Agents; D054713:Bryostatins; D007783:Lactones; D018942:Macrolides; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; C046785:bryostatin 1; D004247:DNA; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate