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

International Journal of Molecular Sciences

Hyun Sook Lee⁵  Han Jin Cho²  Rina Yu³  Ki Won Lee⁴  Hyang Sook Chun¹ 

[1] Food Science and Technology, Chung-Ang University, An-Sung 456-756, Korea; E-Mail:;Department of Food and Nutrition, Hallym University, Chuncheon 200-702, Korea; E-Mails:;Department of Food Science and Nutrition, University of Ulsan, Ulsan 680-749, Korea; E-Mail:;Advanced Institutes of Convergence Technology, Seoul National University, Suwon, Gyonggi-do 443-270, Korea; E-Mail:;Department of Food Science and Nutrition, Dongseo University, 47 Jurye-ro, Sasang-gu, Busan 617-716, Korea; E-Mail:

关键词: kaempferol;    colon cancer;    apoptosis;    mitochondrial pathway;    cell-death receptor pathway;   

DOI  :  10.3390/ijms15022722

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2014 by the authors; licensee MDPI, Basel, Switzerland