Open AccessOkadaic Acid and Phorbol Esters: Comparative Effects of These Tumor Promoters on Cell Transformation, Intercellular Communication and Differentiation in vitro
Author(s) -
Katoh Fumitaka,
Fitzgerald D. James,
Giroldi Laurence,
Fujiki Hirota,
Sugimura Takashi,
Yamasaki Hiroshi
Publication year - 1990
Publication title -
japanese journal of cancer research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 0910-5050
DOI - 10.1111/j.1349-7006.1990.tb02614.x
Subject(s) - okadaic acid , tetradecanoylphorbol acetate , 3t3 cells , intracellular , 12 o tetradecanoylphorbol 13 acetate , cell culture , biology , phorbol , microbiology and biotechnology , cell , biochemistry , transfection , phorbol ester , enzyme , phosphatase , genetics , protein kinase c
Okadaic acid is a non‐12‐O‐tetradecanoylphorbol‐13‐acetate (TPA)‐type tumor promoter in the mouse skin carcinogenesis system. Here we report on the in vitro activity of okadaic acid in 3 assay systems: BALB/c 3T3 cell transformation, gap junctional intercellular communication (GJIC) in various cell types, and inhibition of induction of differentiation of Friend virus‐transformed murine erythroleukemia (MEL) cells. The activity of okadaic acid was compared to that of the phorbol ester tumor promoters TPA and phorbol‐12,13‐didecanoate (PDD). In a test system involving a 2‐week exposure of BALB/c 3T3 cells following 3‐methylcholanthrene initiation, okadaic acid at a concentration of 10 ng/ml was equipotent to PDD as a promoter of cell transformation (4.9 and 3.7 foci/dish, respectively). Longer exposures to okadaic acid resulted in cytotoxicity. Okadaic acid‐generated as well as PDD‐generated transformed foci displayed a selective lack of GJIC between focus cells and surrounding normal cells, i.e., transformed cells communicate among themselves but not with surrounding cells. However, in contrast to TPA, there was no inhibition by okadaic acid, except at toxic doses, of homologous GJIC in BALB/c 3T3 cells or human and mouse keratinocytes. Furthermore, okadaic acid, unlike TPA, did not inhibit MEL cell differentiation. Together, these results indicate that okadaic acid acts as a promoter of cell transformation but that its mechanism of action is different from that of the phorbol ester tumor promoters.