Carbon nanotube based dielectric spectroscopy of tumor secretion; electrochemical lipidomics for cancer diagnosis.

Cell free diagnosis of cancer is one of the crucial fields in new generation of medical technology. In this regard, cancer detection based on coastal fluids secreted from the tissues (named as secretome) has attracted a lot of attention. Lipids are important macromolecules could be found with much higher concentrations in secretome of cancer tissues vs. normal ones. On the other hand, lipids are the main dielectric components of the secretome with respect to proteins and ions. Here for the first time we introduced an electrochemical lipidomics based on electrical impedance spectroscopy (EIS) of the secretomes to detect the cancerous samples due to the lipidic content of their secretions. The EIS sensor was fabricated by multiwall carbon nanotube (MWCNT) arrays as conductive and super hydrophobic materials to have great interactive surface with the lipidic content of the solution. Results of the tests on the secretions of more than 100 human biopsied breast tissues showed the promising match between the charge transfer resistance (RCT) of samples' secretions and pathological states of the tissues with meaningful boundary (up to 8 kΩ for normal and more than 13 kΩ for cancer samples). Mass spectroscopic analyses confirmed the higher content of lipids in cancer secretomes. Electrical lipidomics of the secretome shed new lights in cell free cancer diagnosis and could be applied as a complementary clinical approach in all of biopsy based diagnoses in future.

Bioelectronics of The Cellular Cytoskeleton: Monitoring Cytoskeletal Conductance Variation for Sensing Drug Resistance.

Actin and microtubules form cellular cytoskeletal network, which mediates cell shape, motility and proliferation and are key targets for cancer therapy. Changes in cytoskeletal organization dramatically affect mechanical properties of the cells and correlate with proliferative capacity and invasiveness of cancer cells. Changes in the cytoskeletal network expectedly lead to altered nonmechanical material properties including electrical conductivity as well. Here we applied, for the first time, microtubule and actin based electrical measurement to monitor changes in the electrical properties of breast cancer cells upon administration of anti-tubulin and anti-actin drugs, respectively. Semiconductive behavior of microtubules and conductive behavior of actins presented different bioelectrical responses (in similar frequencies) of the cells treated by anti-tubulin with respect to anti-actin drugs. Doped silicon nanowires were applied as the electrodes due to their enhanced interactive surface and compatibility with electronic fabrication process. We found that treatment with Mebendazole (MBZ), a microtubule destabilizing agent, decreases electrical resistance while treatment with Paclitaxel (PTX), a microtubule stabilizing agent, leads to an increase in electrical resistance. In contrast, actin destabilizing agents, Cytochalasin D (CytD), and actin stabilizing agent, Phalloidin, lead to an increased and decreased electrical resistance, respectively. Our study thus provides proof-of-principle of the usage of determining the electrical function of cytoskeletal compartments in grading of cancer as well as drug resistance assays.

Gallic acid and curcumin induce cytotoxicity and apoptosis in human breast cancer cell MDA-MB-231.

Introduction: Gallic acid (GA) and curcumin (Cur) are natural phenolic compounds that their anti-tumor effects on many types of cancers have been proved. In the current study, the effect of the combination of these agents on MDA-MB-231 breast cancer cells was investigated. Methods: Inhibition of cell proliferation (MTT assay), light microscopy, fluorescence microscopy, cell cycle analysis, nitrite detection, ROS levels, measurement of the mitochondrial membrane potential, GSH level, Annexin V assay, RT-PCR and Western blotting methods were applied. Results: The results revealed the combination of GA and Cur strongly decreased MDA-MB-231 cell growth. Moreover, this combination increased ROS level and cytotoxic activity along with the glutathione depletion in MDA-MB-231 cells. Flow cytometry analysis showed the combination of GA and Cur increased sub-G1 cell population. Furthermore, fluorescent staining and Annexin V/PI assay showed that apoptotic cells were significantly increased in the presence of GA and Cur. At last, protein expression evaluation showed that the combination of GA and Cur significantly decreased Bcl-2 level while increased Bax, cleaved-caspase3 and PARP levels in MDA-MB-231 cells. Conclusion: These results suggest that GA in combination with Cur could be a possible candidate for chemoprevention agent of triple negative breast cancer.

An electrochemical biosensor to distinguish between normal and cancer cells based on monitoring their acidosis using gold-coated silicon Nano-roughened electrode.

One of the most interesting fields of research in cancer diagnosis is tracing the relation between extracellular media and cancer progression. Detecting the secreting contents of the cells and translating these molecular identifications into label-free recognizable patterns would open new opportunities in cancer research. Electrochemical responses are in the range of most attractive sensing mechanisms especially in biochemical approaches. Perturbed ionic exchanges as a known biochemical function of cancer cells presented a strong correlation with the pH of the tumor microenvironment. Different ionic activities detected by an electrochemical bio-sensing system in the malignant and normal cells in the presence of acidic ambient were our main results presented in this research. Herein, silicon Nano-roughened substrate as a well-known electrochemical interface was applied in the construction of the biosensor. Viability rate as well as apoptotic factors involving in cancer progression were assessed by biochemical assays in normal (MCF10A) and cancer (MCF7 and MDA-MB468) breast cells. Our findings demonstrated that pH-based electrochemical responses were matched with the results obtained from the biological analyses of both normal and malignant cells. Induction of acidosis in the cells followed by monitoring their electrochemical responses would be a new trend in microenvironment based cancer investigation.

Cadmium selenide quantum dot-zinc oxide composite: Synthesis, characterization, dye removal ability with UV irradiation, and antibacterial activity as a safe and high-performance photocatalyst.

In this paper, cadmium selenide quantum dot (CdSe QD)-zinc oxide (ZnO) nanocomposite (CdSe QD-ZnO) was synthesized and characterized and its photocatalytic dye degradation ability was investigated. The XRD, FTIR, UV-Vis, AFM and SEM were used to characterize the synthesized nanomaterials. The correlation coefficient of pseudo-first-order kinetic reaction is 0.98. The rate constants from 20 to 30 mg/L of pollutant concentrations was reduced by the order of 0.9. The temporal change in dye concentration reduces as the photocatalyst dosage increase up to optimum value of 0.04 g/L, then beyond that value the increase in the dosage becomes detrimental. Antibacterial activity of the synthesized nanocomposite as a safe photocatalyst was studied in details. Antibacterial activity of as prepared samples was also examined against Escherichia coli (E. coli). For in vitro study, Human umbilical vein endothelial cells (HUVEC) was utilized for the modeling of toxicity of each as prepared samples as representative of human normal cell line. In vivo study was conducted using leeches (Hirudo orientalis). In the presence of ethanol as hydroxyl radical (OH) scavenger, the removal efficiency significantly depresses compared to the di methyl sulfoxide as electron scavengers suggesting OH possesses a major role in photocatalytic dye (Basic Red 18: BR18) decolorization. By coupling with CdSe QD, the zone of inhibition was greatly increased suggesting the size dependent inactivation of E. coli. The results presented that the composite had no significant effect on the proliferation of HUVEC normal cells. In addition, the treatment of cells with ZnO and the composite does not impact on the cell morphology.

Combination of arabinogalactan and curcumin induces apoptosis in breast cancer cells in vitro and inhibits tumor growth via overexpression of p53 level in vivo.

PURPOSE: Increased mortality associated with breast cancer in women has spurred the studies to develop new drugs. Arabinogalactan (AG) and curcumin (Cur) are two natural products broadly explored in cancer therapy. Our major goal in the current study was to assess anticancer properties of combination these reagents in vitro on human breast cancer cells and in vivo utilizing animal model of breast cancer. EXPERIMENTAL DESIGN: We evaluated cell proliferation, apoptosis, cell cycle, and protein expression in vitro on MDA-MB-231 human breast cancer cells. For in vivo studies, murine breast cancer cells were implanted into BALB/c mice. Thereafter, volume of the developing tumor was calculated and expression of Ki67 and p53 proteins was evaluated to analyze cell proliferation and apoptosis. RESULTS: Combination of AG and Cur significantly decreased cell growth in human breast cancer cells without any significant effect on normal cell growth. This combination could increase cell population in sub-G1 phase, which was indicative of apoptosis. Western blotting showed that the combination of AG and Cur significantly increased Bax/Bcl2 ratio as well as cleaved-caspase3 level in MDA-MB-231 cells. Combination of AG and Cur promoted apoptosis by increasing ROS level, changing mitochondrial membrane and reduction of glutathione. In addition, in vivo studies in mouse showed that this combination could inhibit the progression of breast tumors through over-expression of p53 and reduction of Ki67 levels. CONCLUSION: Our findings suggest that the combination of AG and Cur is of great potential to induce apoptosis in breast cancer cells in vitro and in vivo.