Okadaic acid: An additional non-phorbol-12-tetradecanoate-13-acetate-type tumor promoter

Journal Article · Tue Mar 01 04:00:00 EST 1988 · Proceedings of the National Academy of Sciences of the United States of America; (USA)

DOI:https://doi.org/10.1073/pnas.85.6.1768· OSTI ID:6904923

Suganuma, Masami; Fujiki, Hirota; Suguri, Hiroko; Yoshizawa, Shigeru; Hirota, Mitsuru; Nakayasu, Michie ^[1]; Ojika, Makoto; Wakamatsu, Kazumasa; Yamada, Kiyoyuki ^[2]; Sugimura, Takashi ^[3]

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1. National Cancer Center Research Institute, Tokyo (Japan)
2. Nagoya Univ. (Japan)
3. National Cancer Center, Tokyo (Japan)

Okadaic acid is a polyether compound of a C{sub 38} fatty acid, isolated from a black sponge, Halichondria okadai. Previous studies showed that okadaic acid is a skin irritant and induces ornithine decarboxylase in mouse skin 4 hr after its application to the skin. This induction was strongly inhibited by pretreatment of the skin with 13-cis-retinoic acid. A two-stage carcinogenesis experiment in mouse skin initiated by a single application of 100 {mu}g of 7,12-dimethylbenz(a)anthracene (DMBA) and followed by application of 10 {mu}g of okadaic acid twice a week revealed that okadaic acid is a potent additional tumor promoter: tumors developed in 93% of the mice treated with DMBA and okadaic acid by week 16. In contrast, tumors were found in only one mouse each in the groups treated with DMBA alone or okadaic acid alone. An average of 2.6 tumors per mouse was found in week 30 in the group treated with DMBA and okadaic acid. Unlike phorbol 12-tetradecanoate 13-acetate (TPA), teleocidin, and aplysiatoxin, okadaic acid did not inhibit the specific binding of ({sup 3}H)TPA to a mouse skin particulate fraction when added up to 100 {mu}M or activate calcium-activated, phospholipid-dependent protein kinase (protein kinase C) in vitro when added up to 1.2 {mu}M. Therefore, the actions of okadaic acid and phorbol ester may be mediated in different ways. These results show that okadaic acid is a non-TPA-type tumor promoter in mouse skin carcinogenesis.

• OSTI ID: 6904923
• Journal Information: Proceedings of the National Academy of Sciences of the United States of America; (USA), Journal Name: Proceedings of the National Academy of Sciences of the United States of America; (USA) Vol. 85:6; ISSN 0027-8424; ISSN PNASA
• Country of Publication: United States
• Language: English

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59 BASIC BIOLOGICAL SCIENCES
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ALKALINE EARTH METAL COMPOUNDS
ANIMALS
AROMATICS
BIOLOGICAL EFFECTS
BIOLOGICAL PATHWAYS
BODY
CALCIUM COMPOUNDS
CARBON 14 COMPOUNDS
CARBON-CARBON LYASES
CARBOXY-LYASES
CARBOXYLIC ACID ESTERS
CARCINOGENESIS
CARCINOGENS
CONDENSED AROMATICS
DIMETHYLBENZANTHRACENE
DOSE-RESPONSE RELATIONSHIPS
ENZYME INDUCTION
ENZYME INHIBITORS
ENZYMES
ESTERS
GENE REGULATION
HYDROGEN COMPOUNDS
LABELLED COMPOUNDS
LYASES
MAMMALS
MEMBRANE PROTEINS
MICE
ORGANIC COMPOUNDS
ORGANS
PATHOGENESIS
PHORBOL ESTERS
PROMOTERS
PROTEINS
RECEPTORS
RETINOIC ACID
RODENTS
SKIN
TRITIUM COMPOUNDS
TUMOR PROMOTERS
VERTEBRATES