Anthralin, a non-phorbol tumor promoter, fails to inhibit metabolic cooperation in mutant human fibroblasts, but inhibits phytohemagglutinin-induced lymphocyte blastogenesis in vitro.
Two (among many) of the hypotheses put forward to explain mechanisms of action of tumor promoters are: (1) immunosuppression of the host; and (2) inhibition of intercellular junctional communication. Murine spleen cells were exposed for 30 min to various concentrations of anthralin (1,8-dihydroxy-9-anthrone), a polyphenolic non-phorbol promoter, and 1,8-dihydroxyanthraquinone (1,8-DHAQ), an inactive congener. Phytohemagglutinin (PHA)-induced T cell blastogenesis, an indicator of lymphocyte function, was then assessed in vitro. Exposure to anthralin resulted in a concentration-dependent suppression of lymphocyte proliferation with complete suppression occurring at 1 microM. The inactive congener, 1,8-DHAQ, failed to suppress lectin-induced blastogenesis at concentrations up to 10 microM. Dithiothreitol (DTT), a sulfhydryl (SH) compound, failed to protect against the suppression of lymphocyte function by anthralin. In addition, anthralin failed to inhibit in vitro microtubule assembly, a SH-dependent process, in a crude rat brain extract. Finally, unlike 12-O-tetradecanoylphorbol-13-acetate (TPA), the most potent skin tumor promoter known, anthralin failed to inhibit metabolic cooperation between mutant human fibroblasts as assayed by [14C]citrulline incorporation. In summary, the data suggest that anthralin may act as a tumor promoter by suppressing immune parameters, a property which is shared by the phorbol esters.
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Department of Pharmacology and Toxicology, School of Pharmacy and Pharmacal Sciences, Purdue University, West Lafayette, IN 47907.
Pfeifer
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D000818:Animals; D000875:Anthralin / Q000494:pharmacology*; D000880:Anthraquinones / Q000633:toxicity; D002273:Carcinogens; D002450:Cell Communication / Q000187:drug effects; D005260:Female; D005347:Fibroblasts / Q000187:drug effects*; D066298:In Vitro Techniques; D008213:Lymphocyte Activation / Q000187:drug effects*; D008297:Male; D051379:Mice; D008870:Microtubules / Q000187:drug effects; D010835:Phytohemagglutinins / Q000037:antagonists & inhibitors*; D051381:Rats; D011919:Rats, Inbred Strains; D013154:Spleen / Q000187:drug effects
D000880:Anthraquinones; D002273:Carcinogens; D010835:Phytohemagglutinins; D000875:Anthralin; C004315:danthron