Propolis induces cell cycle arrest and apoptosis in human leukemic U937 cells through Bcl-2/Bax regulation. 2008

Muneo Motomura, and Kyung Min Kwon, and Seok-Jong Suh, and Young-Choon Lee, and Yeon-Kye Kim, and In-Seon Lee, and Myung-Sunny Kim, and Dae Young Kwon, and Ikukatsu Suzuki, and Cheorl-Ho Kim
Department of Clinical Nutrition, Suzuka University of Medical Science, 1001-1 Kishioka, Suzuka City, Mie 510-0293, Japan.

We investigated mechanism(s) where propolis induces apoptosis in human leukemic U937 cells. Propolis inhibited the proliferation of U937 cells in a dose-dependent manner by inducing apoptosis and blocking cell cycle progression in the G2/M phase. Western blot analysis showed that propolis increases the expression of p21 and p27 proteins, and decreases the levels of cyclin B1, cyclin A, Cdk2 and Cdc2, thereby contributing to cell cycle arrest. DAPI staining assay revealed typical morphology features of apoptotic cells. Propolis-induced apoptosis was also confirmed by assays with annexin V-FITC, PI-labeling and DNA fragmentation assay. The increase in apoptosis level induced by propolis was associated with down-regulation of Bcl-2 and activation of caspase-3, but not with Bax. These results suggests that propolis-induced apoptosis is related to the selective activation of caspase-3 and induction of Bcl-2/Bax regulation.

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