Thiosulfinates from Allium tuberosum L. induce apoptosis via caspase-dependent and -independent pathways in PC-3 human prostate cancer cells.
This study was aimed to evaluate the apoptotic effects of thiosulfinates purified from Allium tuberosum L. on PC-3 human prostate cancer cells, and to elucidate detailed apoptosis mechanisms. Thiosulfinates significantly decrease viable cell numbers in dose- and time-dependent manners by apoptotic cell death via DNA fragmentation, chromatin condensation, and an increased sub-G1 phase. Apoptosis induced by thiosulfinates is associated with the activation of initiator caspase-8 and -9, and the effector caspase-3. In this study, thiosulfinates stimulated Bid cleavage, indicating that the apoptotic action of caspase-8-mediated Bid cleavage leads to the activation of caspase-9. Thiosulfinates decreased the expression of the anti-apoptotic protein Bcl-2 and increased the expression of the pro-apoptotic protein Bax. Thiosulfinates also increased the expression of AIF, a caspase-independent mitochondrial apoptosis factor, in PC-3 cells. These results indicate that thiosulfinates from A. tuberosum L. inhibit cell proliferation and induce apoptosis in PC-3 cells, which may be mediated via both caspase-dependent and -independent pathways.
Kim
So-Yeon
SY
Department of Food and Nutrition, Sunchon National University, 315 Maegok, Suncheon, Jeonnam 540-742, Republic of Korea.
Park
Kyoung-Wuk
KW
Kim
Jae-Yong
JY
Jeong
Il-Yun
IY
Byun
Myung-Woo
MW
Park
Jung-Eun
JE
Yee
Sung-Tae
ST
Kim
Kee-Hong
KH
Rhim
Johng S
JS
Yamada
Koji
K
Seo
Kwon-Il
KI
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology; D000972:Antineoplastic Agents, Phytogenic / Q000302:isolation & purification / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D051033:Apoptosis Inducing Factor / Q000378:metabolism; D061945:Caspase Inhibitors; D020169:Caspases / Q000378:metabolism*; D048708:Cell Growth Processes / Q000187:drug effects; D045744:Cell Line, Tumor; D027782:Chive / Q000737:chemistry*; D024161:Collagen Type XI / Q000378:metabolism; D004354:Drug Screening Assays, Antitumor; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D008297:Male; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D013441:Sulfinic Acids / Q000302:isolation & purification / Q000494:pharmacology*; D051028:bcl-2-Associated X Protein / Q000378:metabolism
C494829:AIFM1 protein, human; D000590:Amino Acid Chloromethyl Ketones; D000972:Antineoplastic Agents, Phytogenic; D051033:Apoptosis Inducing Factor; C499319:COL11A2 protein, human; D061945:Caspase Inhibitors; D024161:Collagen Type XI; D004791:Enzyme Inhibitors; D010936:Plant Extracts; D019253:Proto-Oncogene Proteins c-bcl-2; D013441:Sulfinic Acids; D051028:bcl-2-Associated X Protein; C096713:benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone; C100040:thiosulfinic acids; D020169:Caspases