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. Method: We investigated the effect of five flavonoids: flavone, kaempferol, morin, myricetin, and quercetin at 1, 10, and 100 μM on proliferation and secretory mediator content (β-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 μM 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 μM increased histamine and tryptase content, but not β-hexosaminidase, equally at days 3 and 4 of culture quercetin also increased the development of secretory granules. Conclusion: These results indicate that certain flavonoids can inhibit HMC-1 proliferation, induce secretory granule development and the accumulation of mediators.