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The antioxidant activity and the association of genistein with carcinogenesis are widely documented. Few studies directly measure the number of free radicals generated in cells, either during the action of factors stimulating their formation, e.g., ultraviolet (UV), or after exposure to antioxidants. The most suitable method for analysing free radicals is electron paramagnetic resonance (EPR) spectroscopy. The EPR method detects a paramagnetic centre with a single electron. Antioxidants neutralize free radicals, therefore, EPR analysis of antioxidant efficacy is as valuable and important as studying the paramagnetic centres of radicals. The aim of the study was to determine the influence of genistein on free radicals basal level and after UV exposure in breast cancer cell lines MCF7, T47D and MDA-MB-231 cell lines. The impact of genistein on cell viability was investigated at concentrations of 0.37 μM, 3.7 μM, 37 μM and 370 μM. Genistein at a concentration of 370 μM revealed a cytotoxic effect on the cells of all three tested breast cancer lines. Genistein at a concentration of 0.37 μM showed no significant effect on the cell viability of all tested breast cancer lines. Therefore, cell proliferation and antioxidant properties were examined using genistein at a concentration of 0.37 μM and 37 μM. X-band (9.3 GHz) EPR spectra of three different types of breast cancer cells (ER-positive, PR-positive and HER-2 negative: MCF7 and T47D and triple-negative MDA-MB-231) were compared. UV irradiation was used as a factor to generate free radicals in cells. The effect of free radical interactions with the antioxidant genistein was tested for non-UV-irradiated (corresponding to the basal level of free radicals in cells) and UV-irradiated cells. The levels of free radicals in the non-irradiated cells studied increased in the following order in breast cancer cells: T47D < MDA-MB-231 < MCF7 and UV-irradiated breast cancer cells: MDA-MB-231 < MCF7 < T47D. UV-irradiation altered free radical levels in all control and genistein-cultured cells tested. UV irradiation caused a slight decrease in the amount of free radicals in MCF7 cells. A strong decrease in the amount of free radicals was observed in UV-irradiated MDA-MB-231 breast cancer cells. The amount of free radicals in T47D cancer cells increased after UV irradiation. Genistein decreased the amount of free radicals in non-irradiated and UV-irradiated MCF7 cells, and only a weak effect of genistein concentrations was reported. Genistein greatly decreased the amount of free radicals in UV-irradiated T47D cancer cells cultured with genistein at a concentration of 3.7 μM. The effect of genistein was negligible in the other samples. Genistein at a concentration of 3.7 μM decreased the amount of free radicals in non-irradiated MDA-MB-231 cancer cells, but genistein at a concentration of 37 μM did not change the amount of free radicals in these cells. An increase in the amount of free radicals in UV-irradiated MDA-MB-231 cancer cells was observed with increasing genistein concentration. The antioxidant efficacy of genistein as a potential plant-derived agent supporting the treatment of various cancers may be determined by differences in signalling pathways that are characteristic of breast cancer cell line subtypes and differences in activation of oxidative stress response pathways.

c-Jun N-terminal kinase (JNK) activation has been shown to play a crucial role in the development of various types of cancer. IQ-1S is a JNK inhibitor based on the 11H-indeno[1,2-b]quinoxalin-11-one scaffold. The aim of this study was to investigate the antiproliferative effect of IQ-1S on MCF7 breast cancer cells in both two-dimensional (2D) monolayer and 3D multicellular spheroid test-systems. Non-adherent, non-tethered 3D objects were generated from single MCF7 breast cancer cells in a hydrogel array. IQ-1S was added directly to the cells seeded in the hydrogel array. MCF7 spheroids were grown for 7 days. Spheroid size, growth rate, and morphology were assessed at single-object resolution. The study revealed significant differences in the size, morphology and some vital characteristics of breast cancer 3D objects when treated with the JNK inhibitor compared to vehicle (dimethyl sulfoxide)-treated controls. Spheroids treated with IQ-1S (20 μM) after 7 days are significantly smaller than the control objects. This difference was not attributable to variations in the initial number of cells seeding for the spheroid formation. Morphological examinations showed that 3D multicellular objects grown from IQ-1S-treated cells lose their regular, round morphology, in contrast to control spheroids. Furthermore, cell proliferation measured using a label-free impedance monitoring platform was reduced in monolayer (2D) culture of MCF7 cells in the presence of 10 and 20 μM IQ-1S. MCF7 cells in 2D culture treated with IQ-1S (20 μM) for 72 and 153 h showed a significant increase in apoptosis as assessed by flow cytometry with annexin V/propidium iodide staining. An in silico evaluation showed that compound IQ-1S has generally satisfactory ADME (absorption, distribution, metabolism, and excretion) properties and high bioavailability. We conclude that IQ-1S effectively inhibits the growth of 3D spheroids and MCF7 cells in 2D culture and has a high potential for use in preclinical tumor growth models.

Introduction: Breast cancer is the second most common cancer in women globally, and the incidence rate has increased annually. Traditional medicine is frequently used as a cancer treatment, and soursop or Annona muricata L (A. muricata) is a traditional medicinal plant that has been widely used as an anticancer treatment and requires more thorough study. Methods: In this research, we prepared ethanol extract and three solvents, ie, ethyl acetate, n-hexane and water fractions of A. muricata leaves and assessed their antiproliferation and cytotoxic activity on MCF7 breast cancer cells compared with that on CV1 normal kidney cells; observation of cell morphology by stained with mixture of propidium iodide and 4',6-diamidino-2-phenylindole indicated that this treatment induced an ongoing process of apoptotic cell death in MCF7 cells. To clarify the cell death mechanism via apoptosis, we assessed the mRNA expression in the caspase cascade of caspase-9, caspase-3, and PARP-1, and anti-apoptotic, Bcl-2 which mediated cytotoxic activity of extracts and ethyl acetate fractions of A. muricata leaves against MCF7 cells. Results: The ethanol extract, ethyl acetate, n-hexane, and water fractions of A. muricata leaves had [IC.sub.50] values of 5.3, 2.86, 3.08, and 48.31 [micro]g /mL, respectively, in MCF7 cells but had no activity in CV1 cells. The high cytotoxic activity of A. muricata leaves was reflected by changes in the morphology of cancer cells that appeared after 6 h exposure to A. muricata leaf extract and ethyl acetate fraction; the membrane and nucleus of cells undergoing apoptosis were characterized by the rupture and loss of membranes and nuclei. The mechanism that mediates this cytotoxic activity in MCF7 cells was mediated through a decrease in the expression of Bcl-2 mRNA and an increase in caspase-9 and caspase-3 mRNA expression. Conclusion: Therefore, the leaves of the medicinal plant A. muricata contained compounds that on extraction exerted a highly effective activity as an anticancer treatment for breast cancer via induced apoptotic cell death. Keywords: soursop, Annona muricata L., MCF7 breast cancer cell, cytotoxicity, caspase-cascade

Background The preventive and therapeutic medical utilization of this plant is an age-long practice across the globe. This study aimed to validate the impact of dark purple blossoms of basil ( Ocimum basilicum L. ) aqueous extract at low temperature (0 °C) mediated mitochondrial fission contributed to induced apoptosis in human breast cancer cells. Methods Fresh blossoms were extracted at low temperature (0 °C) using a watery solvent. Human MCF7 breast cancer cells were then treated with 3 separate fluctuated concentrations of 0, 50, 150 and 250 µg/mL for 24 and 48 h. Results The outcomes demonstrated the presence of anthocyanins, anthraquinones, tannins, reducing sugars, glycosides, proteins, amino acids, flavonoids and volatile oils and nonappearance of Terpinoids and alkaloids. Contrastingly, frail presence of steroids in basil blossoms aqueous concentrate was noted. In addition, the results from a phytochemical subjective examination of basil ( Ocimum basilicum L. ) blossoms aqueous extract demonstrated that most of the credited natural impacts containing more remarkable contents of antioxidants and anticancer compounds in basil blossoms aqueous extract. Moreover, the restraint of glucose take-up was alleviated mediated by a dose-dependent manner in MCF7 cells with basil ( Ocimum basilicum L. ) blossoms aqueous extract inducted for 24 h, resulting in mitochondrial fission. Conclusion This is the first study that shows the impact of the aqueous extract of basil ( Ocimum basilicum L. ) blossoms was extracted at low temperature (0℃/6 h) underlined high amounts of flavonoids and phenolic compounds bearing more anticancer and antioxidant activities compared to another aqueous extract (using boiled water solvent) and alcoholic extracts.

PurposeChemotherapy as an important tool for cancer treatment faces many obstacles such as multidrug resistance and adverse toxic effects on healthy tissues. Drug delivery systems have opened a new window to overcome these problems.MethodsA polyelectrolyte carboxymethyl cellulose polymer as a magnetic nanocarrier was synthesized for enhancing delivery and uptake of doxorubicin in MCF7 breast cancer cells and decreasing the adverse toxic effects to healthy tissues.ResultsThe physicochemical properties of developed nanocarrier showed that it can be used in drug delivery purposes. The efficiency of the delivery system was assessed by loading and release studies. Besides, biological assays including protein-particle interaction, hemolysis assay, cytotoxicity study, cellular uptake, and apoptosis analysis were performed. All results persuaded us to investigate the cytotoxic effects of nanocarrier in an animal model by determining the biochemical parameters attributed to organ injuries, and hematoxylin and eosin (H&E) staining for histopathological manifestations. We observed that the nanocarrier has no toxic effect on healthy tissues, while, it is capable of reducing the toxic side effects of doxorubicin by more cellular internalization.ConclusionChemical characterizations and biological studies confirmed that developed nanocarrier with permanent cationic groups of imidazolium and anionic carboxylic acid groups is an effective candidate for anticancer drug delivery.

Ninety-five structurally diverse chemically synthesized compounds, retrieved from the chemical library of the national research infrastructure OPENSCREEN-GR, were subjected here to a structure-agnostic bioactivity-driven screen focused on putative anti-cancer activities using a number of human cell lines derived from diverse types of cancer. Interestingly, the top four compounds that displayed a broad anti-cancer activity (with no apparent photosensitizing activity) during unbiased biological evaluation were then identified as phenoxazine derivatives. In addition to their cytotoxic activity, phenoxazine derivatives BS115 and ST61 were also found to be cytostatic by inducing a p53-independent G2/M cell cycle arrest as well as a G0/G1 arrest only in cells harboring a functional p53. A kinetics analysis using two multiplex immunoassays and siRNA-mediated knockdown of HSP27 revealed that the latter protein is a key molecule in the response of cancer cells to ST61 via its phosphorylation by p38 MAPK. The main mechanism underlying ST61’s anti-cancer activity was found to involve oxidative stress, as scavenging of ST61-induced reactive oxygen species by N-acetyl-cysteine led to the abrogation of the compound’s cytotoxic effect.

The aim was to evaluate tetraiodothyroacetic acid (tetrac), a thyroid hormone analog of l-thyroxin, conjugated to poly(lactic- -glycolic acid) nanoparticles (T-PLGA-NPs) both and for the treatment of drug-resistant breast cancer. The uptake of tetrac and T-PLGA-NPs in doxorubicin-resistant MCF7 (MCF7-Dx) cells was evaluated using confocal microscopy. Cell proliferation assays and a chick chorioallantoic membrane model of FGF2-induced angiogenesis were used to evaluate the anticancer effects of T-PLGA-NPs. efficacy was examined in a MCF7-Dx orthotopic tumor BALBc nude mouse model. T-PLGA-NPs were restricted from entering into the cell nucleus, and T-PLGA-NPs inhibited angiogenesis by 100% compared with 60% by free tetrac. T-PLGA-NPs enhanced inhibition of tumor-cell proliferation at a low-dose equivalent of free tetrac. treatment with either tetrac or T-PLGA-NPs resulted in a three- to five-fold inhibition of tumor weight. T-PLGA-NPs have high potential as anticancer agents, with possible applications in the treatment of drug-resistant cancer. Original submitted 2 May 2012; Revised submitted 21 November 2012

Background Recent studies have revealed the positive antiproliferative and cytotoxic effects of antiviral agents in cancer treatment. The real effect of adjuvant antiviral therapy is still controversial due to the lack of studies in biochemical mechanisms. Here, we studied the effect of the antiviral agent acyclovir on morphometric and migratory features of the MCF7 breast cancer cell line. Molecular levels of various proteins have also been examined. Methods To evaluate and assess the effect of antiviral treatment on morphometric, migratory and other cellular characteristics of MCF7 breast cancer cells, the following experiments were performed: (i) MTT assay to measure the viability of MCF7 cells; (ii) Colony formation ability by soft agar assay; (iii) Morphometric characterization by immunofluorescent analysis using confocal microscopy; (iv) wound healing and transwell membrane assays to evaluate migration and invasion capacity of the cells; (v) ELISA colorimetric assays to assess expression levels of caspase-3, E-cadherin and enzymatic activity of aldehyde dehydrogenase (ALDH). Results We demonstrate the suppressive effect of acyclovir on breast cancer cells. Acyclovir treatment decreases the growth and the proliferation rate of cells and correlates with the upregulated levels of apoptosis associated cytokine Caspase-3. Moreover, acyclovir inhibits colony formation ability and cell invasion capacity of the cancer cells while enhancing the expression of E-cadherin protein in MCF7 cells. Breast cancer cells are characterized by high ALDH activity and associated with upregulated proliferation and invasion. According to this study, acyclovir downregulates ALDH activity in MCF7 cells. Conclusions These results are encouraging and demonstrate the possibility of partial suppression of cancer cell proliferation using an antiviral agent. Acyclovir antiviral agents have a great potential as an adjuvant therapy in the cancer treatment. However, more research is necessary to identify relevant biochemical mechanisms by which acyclovir induces a potent anti-cancer effect.

The present study investigated the biomedical potential of eco-friendly Citrullus colocynthis-mediated silver nanoparticles (Cc-AgNPs). The antibacterial efficacy of Cc-AgNPs was evaluated against two multidrug-resistant pathogenic bacterial strains, Escherichia coli and Pseudomonas aeruginosa. The antiproliferative and antilipidemic performance of the prepared particles was determined against the MCF7 cell line, a breast cancer cell line. The in vitro antibacterial assay revealed that Cc-AgNPs induced dose-dependent bactericidal activity, as a considerable increase in the zone of inhibition (ZOI) was noted at higher concentrations. Reduced proliferation, migration, spheroid size, and colony formation exhibited the substantial antiproliferative potential of Cc-AgNPs against MCF7 cells. Significant alterations in the expression of cell surface markers, apoptosis, and cell proliferation genes further confirmed the antiproliferative impact of Cc-AgNPs. Moreover, Cc-AgNPs exhibited antilipidemic activity by reducing cellular cholesterol and triglyceride levels and regulating key genes involved in lipogenesis. In conclusion, these results propose that Cc-AgNPs can be employed as a potent tool for future antibacterial and anticancer applications