title: Vitamin C suppresses cell death in MCF-7 human breast cancer cells induced by tamoxifen.
abstract: Vitamin C is generally thought to enhance immunity and is widely taken as a supplement especially during cancer treatment. Tamoxifen (TAM) has both cytostatic and cytotoxic properties for breast cancer. TAM engaged mitochondrial oestrogen receptor beta in MCF-7 cells and induces apoptosis by activation of pro-caspase-8 followed by downstream events, including an increase in reactive oxygen species and the release of pro-apoptotic factors from the mitochondria. In addition to that, TAM binds with high affinity to the microsomal anti-oestrogen-binding site and inhibits cholesterol esterification at therapeutic doses. This study aimed to investigate the role of vitamin C in TAM-mediated apoptosis. Cells were loaded with vitamin C by exposure to dehydroascorbic acid, thereby circumventing in vitro artefacts associated with the poor transport and pro-oxidant effects of ascorbic acid. Pre-treatment with vitamin C caused a dose-dependent attenuation of cytotoxicity, as measured by acridine-orange/propidium iodide (AO/PI) and Annexin V assay after treatment with TAM. Vitamin C dose-dependently protected cancer cells against lipid peroxidation caused by TAM treatment. By real-time PCR analysis, an impressive increase in FasL and tumour necrosis factor-α (TNF-α) mRNA was detected after TAM treatment. In addition, a decrease in mitochondrial transmembrane potential was observed. These results support the hypothesis that vitamin C supplementation during cancer treatment may detrimentally affect therapeutic response.
authors.affiliation: Department of Cell and Molecular Biology, Faculty of Biotechnology and Biomolecular Sciences, Universiti Putra Malaysia, Serdang, Selangor, Malaysia.
authors.forename: Tamilselvan
authors.initials: T
authors.lastname: Subramani
authors.forename: Swee Keong
authors.initials: SK
authors.lastname: Yeap
authors.forename: Wan Yang
authors.initials: WY
authors.lastname: Ho
authors.forename: Chai Ling
authors.initials: CL
authors.lastname: Ho
authors.forename: Abdul Rahman
authors.initials: AR
authors.lastname: Omar
authors.forename: Suraini Abdul
authors.initials: SA
authors.lastname: Aziz
authors.forename: Nik Mohd Afizan Nik Abd
authors.initials: NM
authors.lastname: Rahman
authors.forename: Noorjahan Banu
authors.initials: NB
authors.lastname: Alitheen
mesh_terms: D017304:Annexin A5; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology*; D053181:Caspase 8 / Q000235:genetics / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D003683:Dehydroascorbic Acid / Q000378:metabolism / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D053222:Fas Ligand Protein / Q000235:genetics / Q000378:metabolism; D005260:Female; D006801:Humans; D015227:Lipid Peroxidation / Q000187:drug effects; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D011419:Propidium; D017382:Reactive Oxygen Species / Q000378:metabolism; D013629:Tamoxifen / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
chemical_list: D017304:Annexin A5; D018931:Antineoplastic Agents, Hormonal; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; D013629:Tamoxifen; D011419:Propidium; D053181:Caspase 8; D003683:Dehydroascorbic Acid
keywords: ROS; apoptosis; breast cancer; free radical; lipid peroxidation; tamoxifen; vitamin C