Vegetable-derived isothiocyanates: anti-proliferative activity and mechanism of action.

2.50
Hdl Handle:
http://hdl.handle.net/10146/68519
Title:
Vegetable-derived isothiocyanates: anti-proliferative activity and mechanism of action.
Authors:
Zhang, Yuesheng; Yao, Song; Li, Jun
Abstract:
Many isothiocyanates (ITC), which are available to human subjects mainly through consumption of cruciferous vegetables, demonstrate strong cancer-preventive activity in animal models. Human studies also show an inverse association between consumption of ITC and risk of cancer in several organs. Whereas earlier studies primarily focused on the ability of ITC to inhibit carcinogen-activating enzymes and induce carcinogen-detoxifying enzymes, more recent investigations have shown that ITC inhibit the proliferation of tumour cells both in vitro and in vivo by inducing apoptosis and arresting cell cycle progression. ITC cause acute cellular stress, which may be the initiating event for these effects. These findings shed new light on the mechanism of action of ITC and indicate that ITC may be useful both as cancer-preventive and therapeutic agents. ITC activate caspase 9-mediated apoptosis, apparently resulting from mitochondrial damage, and also activate caspase 8, but the mechanism remains to be defined. Cell cycle arrest caused by ITC occurs mainly in the G2/M phase, and both the G2 and M phases are targetted; critical G2-phase regulators, including cyclin B1, cell division cycle (Cdc) 2 and Cdc25C, are down regulated or inhibited, and tubulin polymerization and spindle assembly are disrupted. Moreover, ITC are metabolized in vivo through the mercapturic acid pathway, giving rise to thiol conjugates (dithiocarbamates). Studies show that these dithiocarbamates are similar to their parent ITC in exerting anti-proliferative activity. Taken together, dietary ITC are highly-promising anti-cancer agents, capable of targetting multiple cellular components that are important for tumour cell survival and proliferation.
Citation:
Proc Nutr Soc 2006, 65 (1):68-75
Journal:
The Proceedings of the Nutrition Society
Issue Date:
Feb-2006
URI:
http://hdl.handle.net/10146/68519
PubMed ID:
16441946
Additional Links:
http://journals.cambridge.org/action/displayAbstract?fromPage=online&aid=814604
Type:
Article
Language:
en
Description:
KEYWORDS - CLASSIFICATION: administration & dosage;Anticarcinogenic Agents;Apoptosis;chemistry;Caspases;Cell Cycle;Chemoprevention;drug effects;dietary modulation of carcinogenesis-related pathways;enzymology;Enzyme Activation;Humans;Isothiocyanates;metabolism;Neoplasms;New York;pharmacology;prevention & control;Research;Vegetables.
ISSN:
0029-6651
Appears in Collections:
Articles with annotation

Full metadata record

DC FieldValue Language
dc.contributor.authorZhang, Yuesheng-
dc.contributor.authorYao, Song-
dc.contributor.authorLi, Jun-
dc.date.accessioned2009-05-19T08:27:30Z-
dc.date.available2009-05-19T08:27:30Z-
dc.date.issued2006-02-
dc.identifier.citationProc Nutr Soc 2006, 65 (1):68-75en
dc.identifier.issn0029-6651-
dc.identifier.pmid16441946-
dc.identifier.urihttp://hdl.handle.net/10146/68519-
dc.descriptionKEYWORDS - CLASSIFICATION: administration & dosage;Anticarcinogenic Agents;Apoptosis;chemistry;Caspases;Cell Cycle;Chemoprevention;drug effects;dietary modulation of carcinogenesis-related pathways;enzymology;Enzyme Activation;Humans;Isothiocyanates;metabolism;Neoplasms;New York;pharmacology;prevention & control;Research;Vegetables.en
dc.description.abstractMany isothiocyanates (ITC), which are available to human subjects mainly through consumption of cruciferous vegetables, demonstrate strong cancer-preventive activity in animal models. Human studies also show an inverse association between consumption of ITC and risk of cancer in several organs. Whereas earlier studies primarily focused on the ability of ITC to inhibit carcinogen-activating enzymes and induce carcinogen-detoxifying enzymes, more recent investigations have shown that ITC inhibit the proliferation of tumour cells both in vitro and in vivo by inducing apoptosis and arresting cell cycle progression. ITC cause acute cellular stress, which may be the initiating event for these effects. These findings shed new light on the mechanism of action of ITC and indicate that ITC may be useful both as cancer-preventive and therapeutic agents. ITC activate caspase 9-mediated apoptosis, apparently resulting from mitochondrial damage, and also activate caspase 8, but the mechanism remains to be defined. Cell cycle arrest caused by ITC occurs mainly in the G2/M phase, and both the G2 and M phases are targetted; critical G2-phase regulators, including cyclin B1, cell division cycle (Cdc) 2 and Cdc25C, are down regulated or inhibited, and tubulin polymerization and spindle assembly are disrupted. Moreover, ITC are metabolized in vivo through the mercapturic acid pathway, giving rise to thiol conjugates (dithiocarbamates). Studies show that these dithiocarbamates are similar to their parent ITC in exerting anti-proliferative activity. Taken together, dietary ITC are highly-promising anti-cancer agents, capable of targetting multiple cellular components that are important for tumour cell survival and proliferation.en
dc.language.isoenen
dc.relation.urlhttp://journals.cambridge.org/action/displayAbstract?fromPage=online&aid=814604en
dc.subjectIsothiocyanateen
dc.subjectAnti-cancer agenten
dc.subjectCancer chemopreventive agenten
dc.subject.meshAnticarcinogenic Agents-
dc.subject.meshApoptosis-
dc.subject.meshCaspases-
dc.subject.meshCell Cycle-
dc.subject.meshEnzyme Activation-
dc.subject.meshHumans-
dc.subject.meshIsothiocyanates-
dc.subject.meshNeoplasms-
dc.subject.meshVegetables-
dc.titleVegetable-derived isothiocyanates: anti-proliferative activity and mechanism of action.en
dc.typeArticleen
dc.identifier.journalThe Proceedings of the Nutrition Societyen
All Items in ECNIS-NIOM are protected by copyright, with all rights reserved, unless otherwise indicated.