Apoptosis in MCF-7 breast cancer cells induced by S-alkenylmercaptocysteine (CySSR) species derived from Allium tissues in combination with sodium selenite.

Abstract

S-Allylmercaptocysteine (CySSA) from garlic is known to exhibit anti-cancer effects. Apoptosis induction by CySSA was contrasted with S-1-propenylmercaptocysteine (CySSPe) (the major onion analog) in the presence of Na2SeO3 (Se) in breast cancer cells MCF-7. The dose of CySSA or CySSPe alone required to reduce viable cells by 50% was >400μM, and this was reduced to 62μM and 91μM for CySSA+Se and CySSPe+Se, respectively, at molar ratios of 39:1. Synergism of the mixtures was confirmed by isobologram analysis and the treatments evoked enhanced thiol efflux from MCF-7 cells. Apoptosis was confirmed by Annexin-V and propidium iodide staining. Cell cycle arrest occurred at the G2/M and sub-G1 interphases. Both CySSR+Se mixtures reduced the levels of Akt. CySSPe+Se elevated GSK-3 protein levels, whereas CySSA+Se did not. CySSR+Se mixtures enhanced phospho-c-Jun levels, with CySSA+Se more potent than CySSPe+Se. Corresponding increases in phospho-p53, Bax and Bad levels were observed, indicating apoptosis occurred via the mitochondrial pathway. Lack of caspases 6/7 activation implicated a caspase-independent pathway for apoptosis. Reduction of imported CySSR and export of thiols by MCF-7 cells facilitates the reduction of selenite to yield H2Se, a cytotoxic agent. This appears to be the first report of an anti-cancer effect of CySSPe.

• Authors: Wei Zhang, Hang Xiao, Kirk L Parkin
• Journal: Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association (Food Chem Toxicol) Vol. 68 Pg. 1-10 (Jun 2014) ISSN: 1873-6351 [Electronic] England
• PMID: 24614136 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier Ltd. All rights reserved.

Chemical References

• Annexin A5
• Antineoplastic Agents
• BAD protein, human
• BAX protein, human
• Plant Extracts
• S-allylmercaptocysteine
• TP53 protein, human
• Tumor Suppressor Protein p53
• bcl-2-Associated X Protein
• bcl-Associated Death Protein
• Proto-Oncogene Proteins c-akt
• Glycogen Synthase Kinase 3
• CASP6 protein, human
• CASP7 protein, human
• Caspase 6
• Caspase 7
• Sodium Selenite
• Cysteine

Topics

• Allium (chemistry)
• Annexin A5 (metabolism)
• Antineoplastic Agents (pharmacology)
• Apoptosis (drug effects)
• Caspase 6 (genetics, metabolism)
• Caspase 7 (genetics, metabolism)
• Cell Cycle Checkpoints (drug effects)
• Cell Survival (drug effects)
• Cysteine (analogs & derivatives, pharmacology)
• Dose-Response Relationship, Drug
• Drug Synergism
• Female
• Glycogen Synthase Kinase 3 (metabolism)
• Humans
• MCF-7 Cells
• Mitochondria (drug effects)
• Plant Extracts (pharmacology)
• Proto-Oncogene Proteins c-akt (genetics, metabolism)
• Signal Transduction
• Sodium Selenite (pharmacology)
• Tumor Suppressor Protein p53 (genetics, metabolism)
• bcl-2-Associated X Protein (genetics, metabolism)
• bcl-Associated Death Protein (genetics, metabolism)