Suppression of Tumor Promoter-induced Oxidative Events and DNA Damage in Vivo by Sarcophytol A: A Possible Mechanism of Antipromotion

Huachen Wei, Krystyna Frenkel

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Sarcophytol A (Sarp A), a nontoxic compound isolated from marine soft coral, inhibits the in vivo effects of tumor promoters. However, the mechanism of its action is unknown. Our studies show that Sarp A suppresses oxidant formation and DNA oxidation in the epidermis of SENCAR mice exposed to 12-0-tetradecanoylphorbol-13-acetate(TPA). In the short-term experiments, mice were topically pretreated with dif ferent doses of Sarp A before 6.5 nmol TPA, and the same treatment was repeated 20 h later. Sarp A significantly decreased the TPA-induced infiltration of neutrophils, the levels of myeloperoxidase in the dermis, and the formation of H2O2, câ«-thymidine glycol, 8-hydroxyl-2'-deoxyguanosine, and 5-hydroxymethyl-2'-deoxyuridine in the epidermis. In the long-term studies, repeated TPA applications (3.2 nmol twice a week for 16 weeks) increased m-thymidine glycol 2.7-fold, 5-hydroxymethyl-2'- deoxyuridine 3.4-fold, and 8-hydroxyl-2'-deoxyguanosine 3.3-fold in ep idermal DNA over the basal levels. Application of 350 nmol Sarp A before each TPA treatment significantly decreased the formation of oxidized DNA bases even below those present in the control mouse skin. Histolã³gica!examination showed that Sarp A also alleviated the TPAinduced inflammatory response and infiltration of phagocytes. Thus, it is possible that suppression of tumor promotion by Sarp A is due (at least in part) to its inhibitory effects on tumor promoter-mediated migration and activation of phagocytes, oxidant formation, and DNA base oxidation.

Original languageEnglish
Pages (from-to)2298-2303
Number of pages6
JournalCancer Research
Issue number8
StatePublished - Apr 1992
Externally publishedYes


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