title: Allyl Isothiocyanate Induces Cell Toxicity by Multiple Pathways in Human Breast Cancer Cells.
abstract: Isothiocyanates (ITCs) occur in many cruciferous vegetables. These compounds, which have significant anticancer actions, can induce apoptosis in different human cancer cell lines. In the present study, we investigated if allyl isothiocyanate (AITC) would induce toxicity in human breast cancer MCF-7 (estrogen receptor positive) and MDA-MB-231 (estrogen receptor negative) cells. We found that AITC stimulated reactive oxygen species and Ca[Formula: see text] production, and decreased the mitochondrial membrane potential. Activity of caspase-8, -9 and -3 was increased by AITC in both cell lines. AITC also induced mitochondrial-mediated apoptosis, as shown by cytochrome c, AIF and Endo G release from mitochondria, activation of caspase-9 and caspase-3, and formation of DAPI-positive cells. There was a significant reduction in the levels of the anti-apoptotic protein Bcl-2 along with a marked increase in the pro-apoptotic protein Bax in both cell lines. AITC induced apoptosis in human breast cancer MCF-7 cells via AIF and Endo G signaling pathways, but in MDA-MB-231 cells apoptosis occurred via the GADD153 pathway. This study has revealed novel anti-cancer mechanisms of AITC, a compound that is ordinarily present in human diets and may have potential therapeutic effects in various cancers.
authors.affiliation: * Departments of Biological Science and Technology.
authors.forename: Peng
authors.initials: P
authors.lastname: Bo
authors.affiliation: † Graduate Institute of Pharmaceutical Chemistry.
authors.forename: Jin-Cherng
authors.initials: JC
authors.lastname: Lien
authors.affiliation: ¶ Department of Chinese-Western Medicine, Chung Shan Medical University Hospital, Taichung 402, Taiwan.|∥ School of Medicine, Chung Shan Medical University, Taichung 402, Taiwan.
authors.forename: Ya-Yin
authors.initials: YY
authors.lastname: Chen
authors.affiliation: ‡ School of Dentistry.
authors.forename: Fu-Shun
authors.initials: FS
authors.lastname: Yu
authors.affiliation: ** Departments of Clinical Pathology, Cheng Hsin General Hospital, Taipei, Taiwan.
authors.forename: Hsu-Feng
authors.initials: HF
authors.lastname: Lu
authors.affiliation: § School of Pharmacy, China Medical University, Taichung 404, Taiwan.
authors.forename: Chun-Shu
authors.initials: CS
authors.lastname: Yu
authors.affiliation: †† Division of Neurosurgical Oncology, Neurological Institute, Taichung Veterans General Hospital, Taichung 407, Taiwan.|‡‡ National Defense Medical Center, Taipei 114, Taiwan.
authors.forename: Yu-Cheng
authors.initials: YC
authors.lastname: Chou
authors.affiliation: § School of Pharmacy, China Medical University, Taichung 404, Taiwan.
authors.forename: Chien-Chih
authors.initials: CC
authors.lastname: Yu
authors.affiliation: * Departments of Biological Science and Technology.|§§ Department of Biotechnology, Asia University, Taichung 413, Taiwan.
authors.forename: Jing-Gung
authors.initials: JG
authors.lastname: Chung
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D019607:Brassicaceae / Q000737:chemistry; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology*; D002118:Calcium / Q000378:metabolism; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D017879:Isothiocyanates / Q000494:pharmacology*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D014675:Vegetables / Q000737:chemistry
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D017879:Isothiocyanates; D017382:Reactive Oxygen Species; D011960:Receptors, Estrogen; C004471:allyl isothiocyanate; D020169:Caspases; D002118:Calcium
keywords: Allyl Isothiocyanate; Cell Toxicity; Estrogen Receptor Negative; Estrogen Receptor Positive; Human Breast Cancer