Open AccessVitamin C suppresses cell death in MCF ‐7 human breast cancer cells induced by tamoxifen
Author(s) -
Subramani Tamilselvan,
Yeap Swee Keong,
Ho Wan Yang,
Ho Chai Ling,
Omar Abdul Rahman,
Aziz Suraini Abdul,
Rahman Nik Mohd. Afizan Nik Abd.,
Alitheen Noorjahan Banu
Publication year - 2014
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.12188
Subject(s) - mcf 7 , apoptosis , propidium iodide , cancer cell , fenretinide , tamoxifen , ascorbic acid , cancer research , antiestrogen , chemistry , annexin , reactive oxygen species , pharmacology , endocrinology , biology , medicine , programmed cell death , biochemistry , breast cancer , cancer , retinoic acid , retinoid , human breast , food science , gene
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) m RNA 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.