title: Natural flavonoids and lignans are potent cytostatic agents against human leukemic HL-60 cells.
abstract: Anti leukemic-cell efficacy of 28 naturally occurring and synthetic flavonoids and 11 naturally occurring lignans on human promyelocytic leukemic cell line HL-60 were examined using MTT assay methods. Differences between anti cell-proliferative activity and cytotoxicity of these compounds were compared with those of 4 clinical anti-cancer agents. Eight of the 28 flavonoids and 4 of the 11 lignans showed considerable suppressive effects on HL-60 cell growth with IC50s ranging from 10-940 ng/ml. Among these compounds, genistein, honokiol, machilin A, matairesinol, and arctigenin had the strongest effects with IC50s less than 100 ng/ml, which were almost equivalent to the effects of current anti-cancer agents. The flavonoid genistein and the lignans, however, showed little or no cytotoxicity against HL-60 cells as assessed by dye exclusion tests (LC50s > 2,900 ng/ml), whereas the regular anti-cancer agents had potent cytotoxicity. All of the flavonoids and lignans, except for machilin A and arctigenin, were less effective against growth of human T lymphocytic leukemia cell line MOLT-4. In addition, the flavonoid and the lignans showed little or no inhibiting activity on mitogen-induced blastogenesis of human peripheral-blood lymphocytes. The lignans and genistein were strongly suppressive against incorporations of [3H]thymidine, [3H]uridine, and [3H]leucine into HL-60 cells. These results showed that some of the naturally occurring flavonoids and lignans inhibited HL-60 cell growth with a non-toxic mechanism, possibly via cessation of DNA, RNA, and/or protein synthesis of the leukemic cells.
authors.affiliation: Department of Clinical Pharmacology, Tokyo College of Pharmacy, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Hirano
authors.forename: M
authors.initials: M
authors.lastname: Gotoh
authors.forename: K
authors.initials: K
authors.lastname: Oka
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D005419:Flavonoids / Q000494:pharmacology*; D006801:Humans; D007930:Leucine / Q000378:metabolism; D015473:Leukemia, Promyelocytic, Acute / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D015458:Leukemia, T-Cell / Q000188:drug therapy / Q000473:pathology; D017705:Lignans / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000187:drug effects; D008214:Lymphocytes / Q000187:drug effects / Q000276:immunology; D013778:Tetrazolium Salts; D013844:Thiazoles; D013936:Thymidine / Q000378:metabolism; D014407:Tumor Cells, Cultured / Q000187:drug effects; D014529:Uridine / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D005419:Flavonoids; D017705:Lignans; D013778:Tetrazolium Salts; D013844:Thiazoles; C022616:thiazolyl blue; D007930:Leucine; D013936:Thymidine; D014529:Uridine