Effects of histamine, H1, H2 and Hic receptor antagonists and alpha-fluoromethylhistidine on the growth of human colorectal cancer in the subrenal capsule assay.
Biogenic amines play an important role in regulating cell proliferation in the normal and neoplastic colon. Elevated histidine decarboxylase (HDC) activity has been measured in human colorectal tumors. H2 antagonists can suppress the growth of colorectal cancer and their inclusion in human therapy has been proposed. We studied the effects of histamine, cimetidine, mepyramine and alpha-fluoromethylhistidine (FMH) on the growth of colorectal tumors in ten patients in the 6-day mouse subrenal capsule assay (SRCA). The effect of the Hic antagonist DPPE was tested in two assays. In summary, a reduction of tumor size was achieved with histamine and DPPE. In addition, significant inhibition of tumor growth was seen in the FMH-treated animals. When pooled by their growth potential, as assessed by the growth of saline-treated controls, FMH and DPPE caused distinct tumor reduction in rapidly growing tumors. In the moderately growing tumors, histamine and mepyramine were the most effective.
Suonio
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E
Department of Pharmacology and Toxicology, University of Kuopio, Finland.
Tuomisto
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L
Alhava
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E
D000818:Animals; D015179:Colorectal Neoplasms / Q000473:pathology*; D004354:Drug Screening Assays, Antitumor; D006632:Histamine / Q000096:biosynthesis / Q000494:pharmacology; D017442:Histamine Agonists / Q000494:pharmacology; D006633:Histamine Antagonists / Q000494:pharmacology*; D006634:Histamine H1 Antagonists / Q000494:pharmacology*; D006635:Histamine H2 Antagonists / Q000494:pharmacology*; D006640:Histidine Decarboxylase / Q000037:antagonists & inhibitors*; D006801:Humans; D008762:Methylhistidines / Q000494:pharmacology*; D051379:Mice; D008815:Mice, Inbred Strains; D010714:Phosphatidylethanolamines / Q000494:pharmacology; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D011968:Receptors, Histamine / Q000187:drug effects / Q000378:metabolism*
D017442:Histamine Agonists; D006633:Histamine Antagonists; D006634:Histamine H1 Antagonists; D006635:Histamine H2 Antagonists; D008762:Methylhistidines; D010714:Phosphatidylethanolamines; D010975:Platelet Aggregation Inhibitors; D011968:Receptors, Histamine; C007510:1,2-dipalmitoyl-3-phosphatidylethanolamine; C028309:alpha-fluoromethylhistidine; D006632:Histamine; D006640:Histidine Decarboxylase