BACKGROUND: The limitations of surgery, radiotherapy, and chemotherapy in cancer treatment and the increase in the application of nanomaterials in the field of biomedicine have promoted the use of nanomaterials in combination with radiotherapy for cancer treatment. OBJECTIVE: To improve the efficiency of cancer treatment, curcumin-naringenin loaded dextran-coated magnetic nanoparticles (CUR-NAR-D-MNPs) were used as chemotherapy and in combination with radiotherapy to verify their effectiveness in treating tumors. METHODS: CUR-NAR-D-MNPs were prepared and studied by several characterization methods. Median inhibitory concentration (IC50) and cellular toxicity were evaluated by 3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide (MTT) assay. The cell death and radiosensitization were studied by acridine orange/ethidium bromide dual staining of MCF-7 human breast cancer cells. RESULTS: CUR-NAR-D-MNPs induce apoptosis and inhibited cell proliferation through reactive oxygen species (ROS) generation. CUR-NAR-D-MNPs used alone had a certain therapeutic effect on tumors. CUR-NAR-D-MNPs plus radiotherapy significantly reduced the tumor volume and led to cell cycle arrest and induction of apoptosis through modulation of P53high, P21high, TNF-αlow, CD44low, and ROShigh signaling CONCLUSIONS: CUR-NAR-D-MNPs are effective in the treatment of tumors when combined with radiotherapy, and show radiosensitization effects against cancer proliferation in vitro and in vivo.
Globally, breast cancer (BC) poses a serious public health risk. The disease exhibits a complex heterogeneous etiology and is associated with a glycolytic and oxidative phosphorylation (OXPHOS) metabolic reprogramming phenotype, which fuels proliferation and progression. Due to the late manifestation of symptoms, rigorous treatment regimens are required following diagnosis. Existing treatments are limited by a lack of specificity, systemic toxicity, temporary remission, and radio-resistance in BC. In this study, we have developed CD44 and folate receptor-targeting multi-functional dual drug-loaded nanoparticles. This composed of hyaluronic acid (HA) and folic acid (FA) conjugated to a 2-deoxy glucose (2DG) shell linked to a layer of dichloroacetate (DCA) and a magnesium oxide (MgO) core (2DG@DCA@MgO; DDM) to enhance the localized chemo-radiotherapy for effective BC treatment. The physicochemical properties of nanoparticles including stability, selectivity, responsive release to pH, cellular uptake, and anticancer efficacy were thoroughly examined. Mechanistically, we identified multiple component signaling pathways as important regulators of BC metabolism and mediators for the inhibitory effects elicited by DDM. Nanoparticles exhibited sustained DDM release properties in a bio-relevant media, which was responsive to the acidic pH enabling eligibility to the control of drug release from nanoparticles. DDM-loaded and HA–FA-functionalized nanoparticles exhibited increased selectivity and uptake by BC cells. Cell-based assays revealed that the functionalized DDM significantly suppressed cancer cell growth and improved radiotherapy (RT) through inducing cell cycle arrest, enhancing apoptosis, and modulating glycolytic and OXPHOS pathways. By highlighting DDM mechanisms as an antitumor and radio-sensitizing reagent, our data suggest that glycolytic and OXPHOS pathway modulation occurs via the PI3K/AKT/mTOR/NF-κB/VEGFlow and P53high signaling pathway. In conclusion, the multi-functionalized DDM opposed tumor-associated metabolic reprogramming via multiple signaling pathways in BC cells as a promising targeted metabolic approach.
Various approaches have been developed for diminishing the effects of radiation on normal tissues or enhancing tumor cell killing by ionizing radiation. Recently, there has been an increase in the interest in research on synthetic and/or natural radioprotective agents. An important potential use for these agents is to modify and improve the outcome of radiation therapy. The aim of this study was to examine the potential radioprotective role and antioxidant potency of the novel synthetic anticancer agent, quinoline sulfonamide (PIQSA) against tissue injury and oxidative stress induced by the exposure to gamma radiation and/or incidence of cancer in experimental animals. Mice (normal and bearing solid tumors) administered PIQSA (0.350 mg/kg body weight ip. three times a week for 21 days. At the last week of 30 days experimental period, an animal group was subjected to three successive doses of γ-radiation each of 2 Gy; another group was treated with combined administration of PIQSA 20 minutes before γ-irradiation. Some biochemical parameters (LPx, GSH, SOD, and CAT in liver homogenates, also plasma lipid profile (total lipids, total cholesterol, total triglycerides (TG), HDLc and LDLc were measured. To examine any adverse effect which could be attained by chemical treatment, liver enzymes (AST, ALT), and kidney function (creatinine and urea) were estimated in blood plasma, in addition to examination of some haematological indexes. The results indicated that the deleterious effects due to exposure to γ-radiation, and/or incidence of cancer on most of the estimated parameters could be controlled to a certain extent by administration of PIQSA to animals prior to irradiation. The results also confirmed that there were no significant adverse effects on mice due to the treatment with this chemical compound
Inhibition of histone deacetylases (HDACs) is emerging as a new strategy in cancer therapy. In the present work a novel pyrimido-quinoline benzene sulfonamide (PIQSA compound) was designed and synthesized postulating its ability to inhibit HDAC enzyme in cancer cells. This study was designed to examine the in vitro anti-tumor efficacy of PIQSA against Ehrlich Ascite carcinoma cells (EAC) and three of the human cancer cell lines (H460), brain (U251) and liver (HepG2). The results of Cytotoxic assays showed that PIQSA exhibited in vitro antitumor activity in a dose dependant manner. The tumor growth delay studies indicating that PIQSA resulted in significant regression in tumor growth, which was more pronounced when PIQSA treatment accompanied with radiation exposure. Also, the efficacy of PIQSA to influence radiation response in Ehrlich solid carcinoma (ESC) tumors was estimated. The results suggest that PIQSA exhibited antitumor activities and strong radioenhancing properties associated with inhibition of HDAC activity, DNA fragmentation followed by apoptotic cell death, preferential cell loss of cells particularly in G1/G0 phase through an apoptotic pathway
Medicinal plants are considered to be bioactives valuable sources of anti-cancer. But these compounds are hydrophobic in nature and thus show decreased bioavailability. To overcome this issue, biocompatible drug delivery agents could be conjugating with these bioactives to improve their therapeutic efficacy. In the present study Curcumin loaded dextran coated Fe3O4NPs was synthesized by chemical precipitation method and coated with Dextran (DEX) using diffusion method. The structural, morphological and the magnetic properties of the prepared materials were studied by using Fourier transform infrared (FT-IR) spectro-scopy, transmission electron microscopy (TEM), X-ray diffraction (XRD), dynamic light scattering (DLS), zeta potential and Vibrating Sample Magnetometer (VSM). The MTT (3-(4,5-dimethylthiahiazol-2-yl)-2,5-diphenyl tetrazolium) assay of CUR loaded dextran coated magnetite nanoparticles (CUR/DEX/Fe3O4)NPs exhibited notable toxicity against MCF7 cells in a dose and time dependant manner. The IC50 values were 177µg/ml and 109µg/ml after 24h and 48h incubation respectively.
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