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.

Nanocrystalline magnesium ferrites (MgFe2O4) were produced with an average grain size of about 20 nm. Their structural, morphological, and magnetic characterizations were studied. The cytotoxic effects of MgFe2O4nanoparticles in various concentrations (25, 50, 100, 200, 400, and 800 μg/mL) against MCF-7 human breast cancer cells were analyzed. MTT assay findings suggest the increased accumulation of apoptotic bodies with the increasing concentration of MgFe2O4nanoparticles in a dose-dependent manner. Flow cytometry analysis shows that MgFe2O4nanoparticles in 800 μg/mL concentration are more cytotoxic compared to vehicle-treated MCF-7 cells and suggests their potential utility as a drug carrier in the treatment of cancer.

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Spinel copper ferrite (CuFe 2 O 4 ) and zinc ferrite (ZnFe 2 O 4 ) nanoparticles were synthesized using a sol-gel self-combustion technique. The structural, functional, morphological and magnetic properties of the samples were investigated by Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), Transmission electron microscopy (TEM) and vibrating sample magnetometry (VSM). XRD patterns conform to the copper ferrite and zinc ferrite formation, and the average particle sizes were calculated by using a transmission electron microscope, the measured particle sizes being 56 nm for CuFe 2 O 4 and 68 nm for ZnFe 2 O 4. Both spinel ferrite nanoparticles exhibit ferromagnetic behavior with saturation magnetization of 31 emug´1 for copper ferrite (50.63 Am 2 /Kg) and 28.8 Am 2 /Kg for zinc ferrite. Both synthesized ferrite nanoparticles were equally effective in scavenging 2,2-diphenyl-1-picrylhydrazyl hydrate (DPPH) free radicals. ZnFe 2 O 4 and CuFe 2 O 4 nanoparticles showed 30.57%˘1.0% and 28.69%˘1.14% scavenging activity at 125 µg/mL concentrations. In vitro cytotoxicity study revealed higher concentrations (>125 µg/mL) of ZnFe 2 O 4 and CuFe 2 O 4 with increased toxicity against MCF-7 cells, but were found to be non-toxic at lower concentrations suggesting their biocompatibility.

BackgroundMorinda citrifolia L. that was reported with immunomodulating and cytotoxic effects has been traditionally used to treat multiple illnesses including cancer. An anthraquinone derived from fruits of Morinda citrifolia L., nordamnacanthal, is a promising agent possessing several in vitro biological activities. However, the in vivo anti-tumor effects and the safety profile of nordamnacanthal are yet to be evaluated.MethodsIn vitro cytotoxicity of nordamnacanthal was tested using MTT, cell cycle and Annexin V/PI assays on human MCF-7 and MDA-MB231 breast cancer cells. Mice were orally fed with nordamnacanthal daily for 28 days for oral subchronic toxicity study. Then, the in vivo anti-tumor effect was evaluated on 4T1 murine cancer cells-challenged mice. Changes of tumor size and immune parameters were evaluated on the untreated and nordamnacanthal treated mice.ResultsNordamnacanthal was found to possess cytotoxic effects on MDA-MB231, MCF-7 and 4T1 cells in vitro. Moreover, based on the cell cycle and Annexin V results, nordamnacanthal managed to induce cell death in both MDA-MB231 and MCF-7 cells. Additionally, no mortality, signs of toxicity and changes of serum liver profile were observed in nordamnacanthal treated mice in the subchronic toxicity study. Furthermore, 50 mg/kg body weight of nordamncanthal successfully delayed the progression of 4T1 tumors in Balb/C mice after 28 days of treatment. Treatment with nordamnacanthal was also able to increase tumor immunity as evidenced by the immunophenotyping of the spleen and YAC-1 cytotoxicity assays.ConclusionNordamnacanthal managed to inhibit the growth and induce cell death in MDA-MB231 and MCF-7 cell lines in vitro and cease the tumor progression of 4T1 cells in vivo. Overall, nordamnacanthal holds interesting anti-cancer properties that can be further explored.

BackgroundBromelain, which is a cysteine endopeptidase commonly found in pineapple stems, has been investigated as a potential anti-cancer agent for the treatment of breast cancer. However, information pertaining to the effects of combining bromelain with existing chemotherapeutic drugs remains scarce. This study aimed to investigate the possible synergistic cytotoxic effects of using bromelain in combination with cisplatin on MDA-MB-231 human breast cancer cells.MethodMDA-MB-231 cells were treated with different concentrations (0.24–9.5 µM) of bromelain or cisplatin alone, as well as four different combinations of these two agents to assess their individual and combination effects after 24 and 48 h. Cell viability was analyzed using an MTT assay. The induction of apoptosis was assessed using cell cycle analysis and an Annexin V-FITC assay. The role of the mitochondrial membrane potential in the apoptotic process was assessed using a JC-1 staining assay. Apoptotic protein levels were assessed by western blot analysis and proteome profiling using an antibody array kit.ResultsSingle-agent treatment with cisplatin or bromelain led to dose- and time-dependent decreases in the viability of the MDA-MB-231 cells at 24 and 48 h. Furthermore, most of the combinations evaluated in this study displayed synergistic effects against MDA-MB-231 cells at 48 h, with combination 1 (bromelain 2 µM + cisplatin 1.5 µM) exhibiting the greatest synergistic effect (P = 0.000). The results of subsequent assays indicated that combination 1 treatment induced apoptosis via mitochondria-mediated pathway. Combination 1 also resulted in significant decreases in the levels of several apoptotic proteins such as Bcl-x and HSP70, compared with bromelain (P = 0.002 and 0.000, respectively) or cisplatin (P = 0.000 and 0.001, respectively) single treatment. Notably, MDA-MB-231 cells treated with combination 1 showed increased levels of the pro-apoptotic proteins Bax compared with those treated with bromelain (P = 0.000) or cisplatin single treatment (P = 0.043).ConclusionBromelain in combination with cisplatin synergistically enhanced the induction of apoptosis in MDA-MB-231 cells.

Manganese ferrite (MnFe 2 O 4 ) magnetic nanoparticles were successfully prepared by a sol-gel self-combustion technique using iron nitrate and manganese nitrate, followed by calcination at 150˝C for 24 h. Calcined sample was systematically characterized by X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), transmission electron microscopy (TEM), and vibrational sample magnetometry (VSM) in order to identify the crystalline phase, functional group, morphology, particle size, shape and magnetic behavior. It was observed that the resultant spinal ferrites obtained at low temperature exhibit single phase, nanoparticle size and good magnetic behavior. The study results have revealed the existence of a potent dose dependent cytotoxic effect of MnFe 2 O 4 nanoparticles against 4T1 cell lines at varying concentrations with IC 50 values of 210, 198 and 171 µg/mL after 24 h, 48 h and 72 h of incubation, respectively. Cells exposed to higher concentrations of nanoparticles showed a progressive increase of apoptotic and necrotic activity. Below 125 µg/mL concentration the nanoparticles were biocompatible with 4T1 cells.

Damnacanthal, an anthraquinone compound, is isolated from the roots of Morinda citrifolia L. (noni), which has been used for traditional therapy in several chronic diseases, including cancer. Although noni has long been consumed in Asian and Polynesian countries, the molecular mechanisms by which it exerts several benefits are starting to emerge. In the present study, the effect of damnacanthal on MCF-7 cell growth regulation was investigated. Treatment of MCF-7 cells with damnacanthal for 72 h indicated an antiproliferative activity. The MTT method confirmed that damnacanthal inhibited the growth of MCF-7 cells at the concentration of 8.2 μg/ml for 72 h. In addition, the drug was found to induce cell cycle arrest at the G1 checkpoint in MCF-7 cells by cell cycle analysis. Damnacanthal induced apoptosis, determined by Annexin V-fluorescein isothiocyanate/propidium iodide (PI) dual-labeling, acridine-orange/PI dyeing and caspase-7 expression. Furthermore, damnacanthal-mediated apoptosis involves the sustained activation of p21, leading to the transcription of p53 and the Bax gene. Overall, the present study provided significant evidence demonstrating that p53-mediated damnacanthal induced apoptosis through the activation of p21 and caspase-7.