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HERO ID
3169076
Reference Type
Journal Article
Title
Mechanisms underlying apoptosis-inducing effects of Kaempferol in HT-29 human colon cancer cells
Author(s)
Lee, HS; Cho, HJ; Yu, R; Lee, KW; Chun, HS; Park, JH
Year
2014
Is Peer Reviewed?
Yes
Journal
International Journal of Molecular Sciences
ISSN:
1422-0067
EISSN:
14220067
Volume
15
Issue
2
Page Numbers
2722-2737
Language
English
PMID
24549175
DOI
10.3390/ijms15022722
Abstract
We previously noted that kaempferol, a flavonol present in vegetables and fruits, reduced cell cycle progression of HT-29 cells. To examine whether kaempferol induces apoptosis of HT-29 cells and to explore the underlying molecular mechanisms, cells were treated with various concentrations (0-60 μmol/L) of kaempferol and analyzed by Hoechst staining, Annexin V staining, JC-1 labeling of the mitochondria, immunoprecipitation, in vitro kinase assays, Western blot analyses, and caspase-8 assays. Kaempferol increased chromatin condensation, DNA fragmentation and the number of early apoptotic cells in HT-29 cells in a dose-dependent manner. In addition, kaempferol increased the levels of cleaved caspase-9, caspase-3 and caspase-7 as well as those of cleaved poly (ADP-ribose) polymerase. Moreover, it increased mitochondrial membrane permeability and cytosolic cytochrome c concentrations. Further, kaempferol decreased the levels of Bcl-xL proteins, but increased those of Bik. It also induced a reduction in Akt activation and Akt activity and an increase in mitochondrial Bad. Additionally, kaempferol increased the levels of membrane-bound FAS ligand, decreased those of uncleaved caspase-8 and intact Bid and increased caspase-8 activity. These results indicate that kaempferol induces the apoptosis of HT-29 cells via events associated with the activation of cell surface death receptors and the mitochondrial pathway.
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