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.

The effect of ascorbic acid on the photophysical properties and photodynamic therapy activities of zinc phthalocyanine-single walled carbon nanotube conjugate on MCF-7 cancer cells

“…5F, Supporting Information and Table 3) left 42 ± 5% and 59 ± 3% of cells viable respectively. Again, this shows that the presence of ascorbic acid in SWCNTs reduces its photothermal effect on MCF-7 cancer cells and the finding from this work supported the earlier report by Subramani et al [24] which stated that AA suppresses cell death induced by tamoxifen in MCF-7 human breast cancer cells. The ability of ascorbic acid in suppressing cell death might be due to their ability to reduce oxidative DNA damage and its role in cell differentiation [68].…”

“…In addition, the intravenous administration of ascorbate in pharmacological concentrations can selectively kill cancer cells [19][20][21][22] due to its ability to generate hydrogen peroxide (H 2 O 2 ) that can further produce free radicals. However, there have been conflicting reports on the role of AA in cancer therapeutics; Kurbacher et al [23] reported that AA improves the anti-neoplastic activity of doxorubicin, cisplatin, and paclitaxel in human breast cancer cells in vitro while studies by Subramani et al [24] stated that AA suppresses cell death in MCF-7 human breast cancer cells induced by tamoxifen. Ascorbic acid is a well-known antioxidant and would be expected to quench singlet oxygen and other ROS required for PDT.…”

Ascorbic acid modulates doxorubicin and cyclophosphamide-induced cytogenetic damages in Sarcoma 180 cells

“…In vitro studies with human MCF-7, AA exposure causes attenuation of antineoplastic activity and may affect the therapeutic response [15]. There are also reports indicating that AA can enhance the effectiveness of chemotherapeutic agents that can reduce the cytotoxicity of anticancer drugs, and also may prevent free radicals and neutralize some carcinogens [14,46,47].…”

“…In vitro studies of human MCF-7, vitamin C exposure causes attenuation of antineoplastic, it may affect the therapeutic response [15]. There are also reports that indicate high doses of ascorbic acid, increasing apoptosis in Sarcoma 180 cells on mice co-treated with paclitaxel, enhancing the effects of anticancer [20].…”

“…Most patients in chemotherapy make supplementation with vitamins, especially, vitamin C, due to its high antioxidant capacity, which may cause antagonistic effects to antineoplastic and neutralize some carcinogens [14,15]. Antioxidants such as vitamin C compose the human diet [16], which not only sequester free radicals, but also regulate DNA repair enzymes and post-transcriptional factors [17].…”