Natural flavonoids and lignans are potent cytostatic agents against human leukemic HL-60 cells

Life Sci. 1994;55(13):1061-9. doi: 10.1016/0024-3205(94)00641-5.


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.

Publication types

  • Comparative Study

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Cell Division / drug effects
  • Drug Screening Assays, Antitumor
  • Flavonoids / pharmacology*
  • Humans
  • Leucine / metabolism
  • Leukemia, Promyelocytic, Acute / drug therapy*
  • Leukemia, Promyelocytic, Acute / metabolism
  • Leukemia, Promyelocytic, Acute / pathology
  • Leukemia, T-Cell / drug therapy
  • Leukemia, T-Cell / pathology
  • Lignans / pharmacology*
  • Lymphocyte Activation / drug effects
  • Lymphocytes / drug effects
  • Lymphocytes / immunology
  • Tetrazolium Salts
  • Thiazoles
  • Thymidine / metabolism
  • Tumor Cells, Cultured / drug effects
  • Uridine / metabolism


  • Antineoplastic Agents
  • Flavonoids
  • Lignans
  • Tetrazolium Salts
  • Thiazoles
  • thiazolyl blue
  • Leucine
  • Thymidine
  • Uridine