title: Mechanisms of thiosulfinates from Allium tuberosum L.-induced apoptosis in HT-29 human colon cancer cells.
abstract: This study was performed to elucidate the apoptotic pathways by thiosulfinates, major biologically active components of Allium tuberosum L., in HT-29 human colon cancer cells. Thiosulfinates significantly induced cell death in dose- and time-dependent manners in HT-29 cells, which is associated with apoptosis. Thiosulfinates activated the initiator caspase-8, and -9, and the effector caspase-3. In the present study, thiosulfinates were found to stimulate Bid cleavage, indicating that the apoptotic action of caspase-8-mediated Bid cleavage leads to the activation of caspase-9. Thiosulfinates down-regulated the expression of the anti-apoptotic protein Bcl-2, and up-regulated the expression of the pro-apoptotic protein Bax. We also found that thiosulfinates increased the expression of AIF, a caspase-independent mitochondrial apoptosis factor, and induced DNA fragmentation and chromatin condensation in HT-29 cells. These results indicate that thiosulfinates from A. tuberosum L. inhibited cell proliferation and activated both the caspase-dependent and caspase-independent apoptotic pathways in HT-29 cells.
authors.affiliation: Department of Bioscience and Biotechnology, Kyushu University, Fukuoka 812-8581, Japan.
authors.forename: Ju-Hye
authors.initials: JH
authors.lastname: Lee
authors.forename: Hee-Sun
authors.initials: HS
authors.lastname: Yang
authors.forename: Kyoung-Wuk
authors.initials: KW
authors.lastname: Park
authors.forename: Jae-Yong
authors.initials: JY
authors.lastname: Kim
authors.forename: Mi-Kyung
authors.initials: MK
authors.lastname: Lee
authors.forename: Il-Yun
authors.initials: IY
authors.lastname: Jeong
authors.forename: Ki-Hwan
authors.initials: KH
authors.lastname: Shim
authors.forename: Young-Sook
authors.initials: YS
authors.lastname: Kim
authors.forename: Koji
authors.initials: K
authors.lastname: Yamada
authors.forename: Kwon-Il
authors.initials: KI
authors.lastname: Seo
mesh_terms: D016588:Anticarcinogenic Agents / Q000302:isolation & purification / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D051033:Apoptosis Inducing Factor / Q000096:biosynthesis; D053470:Caspases, Effector / Q000096:biosynthesis; D053471:Caspases, Initiator / Q000096:biosynthesis; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D027782:Chive / Q000737:chemistry*; D003110:Colonic Neoplasms / Q000473:pathology / Q000517:prevention & control; D053938:DNA Fragmentation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006801:Humans; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D013441:Sulfinic Acids / Q000302:isolation & purification / Q000494:pharmacology*; D013997:Time Factors; D051028:bcl-2-Associated X Protein / Q000096:biosynthesis
chemical_list: C494829:AIFM1 protein, human; D016588:Anticarcinogenic Agents; D051033:Apoptosis Inducing Factor; C494826:BAX protein, human; D019253:Proto-Oncogene Proteins c-bcl-2; D013441:Sulfinic Acids; D051028:bcl-2-Associated X Protein; C100040:thiosulfinic acids; D053470:Caspases, Effector; D053471:Caspases, Initiator