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Vitamin C suppresses cell death in MCF-7 human breast cancer cells induced by tamoxifen


Subramani, Tamilselvan and Yeap, Swee Keong and Ho, Wan Yang and Ho, Chai Ling and Omar, Abdul Rahman and Abdul Aziz, Suraini and Nik Abd. Rahman, Nik Mohd. Afizan and Mohamed Alitheen, Noorjahan Banu (2014) Vitamin C suppresses cell death in MCF-7 human breast cancer cells induced by tamoxifen. Journal of Cellular and Molecular Medicine, 18 (2). pp. 305-313. ISSN 1582-1838; ESSN: 1582-4934


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.

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Additional Metadata

Item Type: Article
Divisions: Faculty of Biotechnology and Biomolecular Sciences
Institute of Bioscience
DOI Number: https://doi.org/10.1111/jcmm.12188
Publisher: Wiley-Blackwell Publishing
Keywords: Vitamin C; Tamoxifen; Breast cancer; ROS; Free radical; Apoptosis; Lipid peroxidation
Depositing User: Nurul Ainie Mokhtar
Date Deposited: 12 Feb 2016 07:21
Last Modified: 12 Feb 2016 07:21
Altmetrics: http://www.altmetric.com/details.php?domain=psasir.upm.edu.my&doi=10.1111/jcmm.12188
URI: http://psasir.upm.edu.my/id/eprint/35992
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