Flavones inhibit proliferation and increase mediator content in human leukemic mast cells (HMC-1).
OBJECTIVE
Mast cells are involved in allergic and inflammatory reactions. These cells are also increased in the bone marrow, skin, and other organs in systemic mastocytosis. Flavonoids are naturally occurring molecules with antioxidant, cytoprotective, and anti-inflammatory activities. Some flavonoids, like quercetin, inhibit the growth of certain malignant cells in culture. Quercetin also inhibits histamine release and induces accumulation of secretory granules in rat basophilic leukemia cells.


METHODS
We investigated the effect of five flavonoids: flavone, kaempferol, morin, myricetin, and quercetin at 1, 10, and 100 microM on proliferation and secretory mediator content (beta-hexosaminidase, histamine, and tryptase) in human leukemic mast cells (HMC-1), the doubling time of which was about 2 d.


RESULTS
Flavone and kaempferol at 100 microM inhibited cell proliferation over 80% on either day 3, 4, or 5 of culture. Quercetin showed this level of inhibition only on day 5, myricetin inhibited by 50% at days 3-5, whereas morin's inhibition was < 20%. All flavonoids (except morin) at 100 microm increased histamine and tryptase content, but not beta-hexosaminidase, equally at days 3 and 4 of culture quercetin also increased the development of secretory granules.


CONCLUSIONS
These results indicate that certain flavonoids can inhibit HMC-1 proliferation, induce secretory granule development and the accumulation of mediators.
Alexandrakis
Michael
M
Department of Hematology, Medical Division, School of Health Sciences, University of Crete, Heraklion, Crete, Greece.
Letourneau
Richard
R
Kempuraj
Durajisamy
D
Kandere-Grzybowska
Kristiana
K
Huang
Man
M
Christodoulou
Spyridon
S
Boucher
William
W
Seretakis
Dimitris
D
Theoharides
Theoharis C
TC
D002455:Cell Division / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D047309:Flavones; D005419:Flavonoids / Q000494:pharmacology*; D006632:Histamine / Q000032:analysis*; D006801:Humans; D044949:Kaempferols / Q000494:pharmacology; D007946:Leukemia, Mast-Cell; D008407:Mast Cells / Q000737:chemistry / Q000187:drug effects* / Q000648:ultrastructure; D008854:Microscopy, Electron; D011794:Quercetin / Q000494:pharmacology; D022142:Secretory Vesicles / Q000187:drug effects; D012697:Serine Endopeptidases / Q000032:analysis*; D053802:Tryptases; D014407:Tumor Cells, Cultured; D001619:beta-N-Acetylhexosaminidases / Q000032:analysis*
D047309:Flavones; D005419:Flavonoids; D044949:Kaempferols; C006552:kaempferol; C040015:myricetin; D006632:Histamine; C008548:morin; D011794:Quercetin; D001619:beta-N-Acetylhexosaminidases; D012697:Serine Endopeptidases; C509223:Tpsab1 protein, rat; C509221:Tpsb2 protein, rat; D053802:Tryptases; C043562:flavone