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Apoptosis Induction of Human Leukemia U937 Cells by 7,8-dihydroxyflavone Hydrate Through Modulation of the Bcl-2 Family of Proteins and the MAPKs Signaling Pathway

Apoptosis Induction of Human Leukemia U937 Cells by 7,8-dihydroxyflavone Hydrate Through Modulation of the Bcl-2 Family of Proteins and the MAPKs Signaling Pathway

Hye Young Park, Gi-Young Kim, Taeg Kyu Kwon, Hye Jin Hwang, Nam Deuk Kim, Young Hyun Yoo, Yung Hyun Choi

Mutat Res. 2013 Mar 18;751(2):101-8.

PMID: 23262352

Abstract:

The present study investigated possible mechanisms of apoptosis induction of U937 human leukemic cells by 7,8-dihydroxyflavone hydrate (7,8-DHF), a member of the flavonoid family and a recently identified tyrosine kinase receptor B (TrkB) agonist. 7,8-DHF treatment of U937 cells resulted in inhibition of growth and induction of apoptosis as measured by MTT assay, fluorescence microscopy, DNA fragmentation, and flow cytometry analysis. 7,8-DHF-induced apoptosis in U937 cells was correlated with the up-regulation of death receptor related protein levels and down-regulation of anti-apoptotic IAP family proteins. The increase in apoptosis was also associated with proteolytic activation of caspases, Bid cleavage, insertion of pro-apoptotic Bax into the mitochondria and release of cytochrome c from mitochondria to cytosol. Furthermore, it was found that Bcl-2 overexpression markedly protected U937 cells from 7,8-DHF-induced apoptosis by restoring activation of caspases. In addition, 7,8-DHF treatment effectively activated the mitogen-activated protein kinases (MAPK), and inhibitors of extracellular-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK), but not p38 MAPK, which significantly reduced 7,8-DHF-induced apoptosis. Taken together, our results indicate that the JNK and ERK pathways, and modulation of Bcl-2 family proteins were key regulators of apoptosis in response to 7,8-DHF in U937 cells.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
ALP38183038	7,8-Dihydroxyflavone hydrate		38183-03-8 (anhydrous)	Price

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