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Int. J. Mol. Sci. 2014, 15(2), 2722-2737; doi:10.3390/ijms15022722
Article

Mechanisms Underlying Apoptosis-Inducing Effects of Kaempferol in HT-29 Human Colon Cancer Cells

1,†
, 2,5,†
, 3
, 4,5
, 6
 and 2,4,*
Received: 24 December 2013; in revised form: 4 February 2014 / Accepted: 8 February 2014 / Published: 17 February 2014
(This article belongs to the Section Molecular Pathology)
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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.
Keywords: kaempferol; colon cancer; apoptosis; mitochondrial pathway; cell-death receptor pathway kaempferol; colon cancer; apoptosis; mitochondrial pathway; cell-death receptor pathway
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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MDPI and ACS Style

Lee, H.S.; Cho, H.J.; Yu, R.; Lee, K.W.; Chun, H.S.; Park, J.H.Y. Mechanisms Underlying Apoptosis-Inducing Effects of Kaempferol in HT-29 Human Colon Cancer Cells. Int. J. Mol. Sci. 2014, 15, 2722-2737.

AMA Style

Lee HS, Cho HJ, Yu R, Lee KW, Chun HS, Park JHY. Mechanisms Underlying Apoptosis-Inducing Effects of Kaempferol in HT-29 Human Colon Cancer Cells. International Journal of Molecular Sciences. 2014; 15(2):2722-2737.

Chicago/Turabian Style

Lee, Hyun S.; Cho, Han J.; Yu, Rina; Lee, Ki W.; Chun, Hyang S.; Park, Jung H.Y. 2014. "Mechanisms Underlying Apoptosis-Inducing Effects of Kaempferol in HT-29 Human Colon Cancer Cells." Int. J. Mol. Sci. 15, no. 2: 2722-2737.


Int. J. Mol. Sci. EISSN 1422-0067 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert