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.
Japanese encephalitis (JE) is a neurotropic flavivirus that causes inflammation in central nervous system (CNS), neuronal death and also compromises the structural and functional integrity of the blood-brain barrier (BBB). The aim of this study was to evaluate the BBB disruption and apoptotic process in Japanese encephalitis virus (JEV)-infected transfected human brain microvascular endothelial cells (THBMECs). THBMECs were overlaid by JEV with different MOIs (0.5, 1.0, 5.0 and 10.0) and monitored by electrical cell-substrate impedance sensing (ECIS) in a real-time manner in order to observe the barrier function of THBMECs. Additionally, the level of 43 apoptotic proteins was quantified in the virally infected cells with different MOIs at 24h post infection. Infection of THBMEC with JEV induced an acute reduction in transendothelial electrical resistance (TEER) after viral infection. Also, significant up-regulation of Bax, BID, Fas and Fasl and down-regulation of IGFBP-2, BID, p27 and p53 were observed in JEV infected THBMECs with 0.5 and 10 MOIs compared to uninfected cells. Hence, the permeability of THBMECs is compromised during the JEV infection. In addition high viral load of the virus has the potential to subvert the host cell apoptosis to optimize the course of viral infection through deactivation of pro-apoptotic proteins.