Mechanisms of thiosulfinates from Allium tuberosum L.-induced apoptosis in HT-29 human colon cancer cells.
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.
Lee
Ju-Hye
JH
Department of Bioscience and Biotechnology, Kyushu University, Fukuoka 812-8581, Japan.
Yang
Hee-Sun
HS
Park
Kyoung-Wuk
KW
Kim
Jae-Yong
JY
Lee
Mi-Kyung
MK
Jeong
Il-Yun
IY
Shim
Ki-Hwan
KH
Kim
Young-Sook
YS
Yamada
Koji
K
Seo
Kwon-Il
KI
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
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