Synergistic Effect of Quercetin Magnetite Nanoparticles and Targeted Radiotherapy in Treatment of Breast Cancer.

Quercetin is a potent cancer therapeutic agent present in fruits and vegetables. The pharmaceutical uses of quercetin are limited due to many problems associated with low solubility, bioavailability, permeability, and instability. In addition, the high doses of quercetin show toxic effects in clinical and experimental studies. Therefore, a new strategy is warranted to overcome these problems without the use of toxic doses. The iron oxide nanoparticles can be used as a drug delivery system. This study aimed to prepare quercetin-conjugated magnetite nanoparticles (QMNPs) using biological simple nanoprecipitation and mediated by fungus Aspergillus oryzae. Also, we initiated in vitro and in vivo studies to determine whether QMNPs might sensitize breast cancer to radiotherapy treatment. The structural, morphological, and magnetic properties of the prepared nanoparticles were studied. The results indicated that QMNPs were spherical in shape and 40 nm in diameter. The in vitro studies showed that the incubation of MCF-7, HePG-2, and A459 cancer cells with QMNPs for 24 h effectively inhibited the growth of cancer cell lines in a concentration-dependent manner with IC50 values of 11, 77.5, and104 nmol/mL, respectively. The combination of QMNPs with irradiation (IR) potently blocked MCF-7 cancer cell proliferation and showed significant changes in the morphology of these cells as observed by bright-field inverted light microscopy. Focusing on the long-term toxicity of QMNPs (20 ml/kg), the assessment of hematological, hepatic, and renal markers indicated no toxic effect. Besides, QMNPs inhibited tumor growth and potently enhanced the lateral radiotherapy treatment in N-methyl-N-nitrosourea (MNU)-induced breast cancer in female white albino rats. These anticancer and radiosensitizing activities were ascribed to cytotoxicity, cell cycle arrest, immunomodulation, and efficiency through induction of apoptosis. In a conclusion, these observations suggest that the QMNPs combined with LRT could act as a potential targeted therapy in breast cancer.

Modulatory effect of a new benzopyran derivative via COX-2 blocking and down regulation of NF-κB against γ-radiation induced- intestinal inflammation.

Radiotherapy is considered as a primary modality for cancer treatment which accompanied by several side effects. Protection of normal tissues from radiation effects is one of the most significant concerns for researchers. Although many compounds acting as radio protectors, only two compounds were licensed clinically. Cyclooxygenase-2 (COX-2), as an inflammatory mediator is associated with ROS production with a NF-κB gene up regulation dependent manner in normal tissues. To that extend, his study was designed to target COX-2 and NF-κB by a newly synthesized benzopyran-4-one or chromone derivative; (2E)-2-((4-oxo-4H-chromen-3-yl) methylene amino-4- nitrobenzoic acid (Ch). Exposure of mice to IRR significantly induced intestinal inflammation via overexpression of COX-2 and NF-κB which is accompanied by an increase in the levels of MDA and iNOS in tissue homogenate and in the production of TNF-α and IL-6 as inflammatory signs. Moreover, the apoptotic effect of IRR was manifested by obvious elevation in caspase-3. Interapretonial injection of Ch significantly controls the inflammatory response by blocking the COX-2 and decrease the expression NF-κB which subsequently decreases other inflammatory parameters. Thus Ch compound might be a promising nonsteroidal anti-inflammatory drug (NSAID) against radiation-induced inflammation with a specific mode of COX-2 inhibition. Further researches are needed to elucidate its molecular mechanism and its combination with radiotherapy as a protector.

Phytochemical Investigation, Antitumor Activity, and Hepatoprotective Effects of Acrocarpus fraxinifolius Leaf Extract.

Preclinical Research Nine known phenolic compounds were isolated from an aqueous methanolic extract of Acrocarpus fraxinifolius Weight and Arn leaves (AFL) family Fabaceae. This extract of AFL contained approximately 169 mg gallic acid/g as assessed by HPLC. The AFL extract had marginal antitumor activity (IC50 > 200 µL/mL) but showed a concentration-dependent hepatoprotective effect against CCl4 -induced hepatotoxicity in vitro. Cell viability was increased, ALT and AST activity declined and reduced GSH concentration and SOD activity were restored as compared with silymarin. In vivo concurrent administration of AFL extract (500 mg/kg po) showed a hepatoprotective effect against gamma irradiation and CCl4 as evidenced by reduction of TNF-α, interleukin-6, malondialdehyde, nitric oxide, DNA fragmentation, caspase-3 activity, and downregulation of its m-RNA level and decreased proapoptotic protein Bax expression. AFL extract enhanced glutathione peroxidase, superoxide dismutase, and catalase activities, reduced glutathione concentrations and upregulated the expression of antiapoptotic Bcl-2. The extract could ameliorate hepatic injuries induced by gamma irradiation and CCl4 in rats suggesting potent hepatoprotective activity. Drug Dev Res 78 : 210-226, 2017. © 2017 Wiley Periodicals, Inc.