title: Mechanisms underlying apoptosis-inducing effects of Kaempferol in HT-29 human colon cancer cells.
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.
authors.affiliation: Department of Food Science and Nutrition, Dongseo University, 47 Jurye-ro, Sasang-gu, Busan 617-716, Korea. hyunlee@gdsu.dongseo.ac.kr.
authors.forename: Hyun Sook
authors.initials: HS
authors.lastname: Lee
authors.affiliation: Department of Food and Nutrition, Hallym University, Chuncheon 200-702, Korea. hanjini@hallym.ac.kr.
authors.forename: Han Jin
authors.initials: HJ
authors.lastname: Cho
authors.affiliation: Department of Food Science and Nutrition, University of Ulsan, Ulsan 680-749, Korea. rinayu@ulsan.ac.kr.
authors.forename: Rina
authors.initials: R
authors.lastname: Yu
authors.affiliation: Advanced Institutes of Convergence Technology, Seoul National University, Suwon, Gyonggi-do 443-270, Korea. kiwon@snu.ac.kr.
authors.forename: Ki Won
authors.initials: KW
authors.lastname: Lee
authors.affiliation: Food Science and Technology, Chung-Ang University, An-Sung 456-756, Korea. hschun@cau.ac.kr.
authors.forename: Hyang Sook
authors.initials: HS
authors.lastname: Chun
authors.affiliation: Department of Food and Nutrition, Hallym University, Chuncheon 200-702, Korea. kiwon@snu.ac.kr.
authors.forename: Jung Han Yoon
authors.initials: JH
authors.lastname: Park
mesh_terms: D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000633:toxicity*; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000737:chemistry / Q000378:metabolism; D053179:Caspase 7 / Q000737:chemistry / Q000378:metabolism; D053181:Caspase 8 / Q000737:chemistry / Q000378:metabolism; D053453:Caspase 9 / Q000737:chemistry / Q000378:metabolism; D003110:Colonic Neoplasms / Q000378:metabolism / Q000473:pathology; D045304:Cytochromes c / Q000378:metabolism; D053938:DNA Fragmentation / Q000187:drug effects; D019073:HT29 Cells; D006801:Humans; D044949:Kaempferols / Q000633:toxicity*; D008928:Mitochondria / Q000378:metabolism; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051020:bcl-X Protein / Q000378:metabolism
chemical_list: D000590:Amino Acid Chloromethyl Ketones; D000970:Antineoplastic Agents; D044949:Kaempferols; D051020:bcl-X Protein; C096713:benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone; C006552:kaempferol; D045304:Cytochromes c; D011065:Poly(ADP-ribose) Polymerases; D051057:Proto-Oncogene Proteins c-akt; D053148:Caspase 3; D053179:Caspase 7; D053181:Caspase 8; D053453:Caspase 9