Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adenocarcinoma / drug therapy*
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Adenocarcinoma / metabolism
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Adenocarcinoma / pathology
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Amino Acid Chloromethyl Ketones / pharmacology
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Antineoplastic Agents, Phytogenic / isolation & purification
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Antineoplastic Agents, Phytogenic / pharmacology
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Apoptosis / drug effects*
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Apoptosis / physiology
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Apoptosis Inducing Factor / metabolism
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Caspase Inhibitors
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Caspases / metabolism*
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Cell Growth Processes / drug effects
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Cell Line, Tumor
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Chive / chemistry*
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Collagen Type XI / metabolism
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Drug Screening Assays, Antitumor
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Enzyme Activation
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Enzyme Inhibitors / pharmacology
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Humans
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Male
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Mitochondria / drug effects
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Mitochondria / metabolism
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Plant Extracts / isolation & purification
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Plant Extracts / pharmacology
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Prostatic Neoplasms / drug therapy*
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Prostatic Neoplasms / metabolism
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Prostatic Neoplasms / pathology
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Proto-Oncogene Proteins c-bcl-2 / metabolism
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Sulfinic Acids / isolation & purification
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Sulfinic Acids / pharmacology*
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bcl-2-Associated X Protein / metabolism
Substances
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AIFM1 protein, human
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Amino Acid Chloromethyl Ketones
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Antineoplastic Agents, Phytogenic
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Apoptosis Inducing Factor
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COL11A2 protein, human
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Caspase Inhibitors
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Collagen Type XI
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Enzyme Inhibitors
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Plant Extracts
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Proto-Oncogene Proteins c-bcl-2
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Sulfinic Acids
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bcl-2-Associated X Protein
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benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone
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thiosulfinic acids
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Caspases