Next Article in Journal
ScChi, Encoding an Acidic Class III Chitinase of Sugarcane, Confers Positive Responses to Biotic and Abiotic Stresses in Sugarcane
Previous Article in Journal
E26 Transformation-Specific-1 (ETS1) and WDFY Family Member 4 (WDFY4) Polymorphisms in Chinese Patients with Rheumatoid Arthritis
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,*
1 Department of Food Science and Nutrition, Dongseo University, 47 Jurye-ro, Sasang-gu, Busan 617-716, Korea 2 Department of Food and Nutrition, Hallym University, Chuncheon 200-702, Korea 3 Department of Food Science and Nutrition, University of Ulsan, Ulsan 680-749, Korea 4 Advanced Institutes of Convergence Technology, Seoul National University, Suwon, Gyonggi-do 443-270, Korea 5 WCU Biomodulation Major, Department of Agricultural Biotechnology and Center for Food and Bioconvergence, Seoul National University, Seoul 151-921, Korea 6 Food Science and Technology, Chung-Ang University, An-Sung 456-756, Korea These authors contributed equally to this work.
* Author to whom correspondence should be addressed.
Received: 24 December 2013 / Revised: 4 February 2014 / Accepted: 8 February 2014 / Published: 17 February 2014
(This article belongs to the Section Biochemistry, Molecular Biology and Biophysics)
View Full-Text   |   Download PDF [568 KB, uploaded 19 June 2014]   |  

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 (CC BY 3.0).
SciFeed

Share & Cite This Article

Further Mendeley | CiteULike
Export to BibTeX |
EndNote |
RIS
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.

View more citation formats

Related Articles

Article Metrics

For more information on the journal, click here

Comments

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