Monitoring the mechanism of anti-cancer agents to inhibit colorectal cancer cell proliferation: Enzymatic biosensing of glucose combined with molecular docking.

Glucose, a major energy source in cellular metabolism, has a significant role in cell growth. The increase in glucose uptake is a distinguishing hallmark in cancer cells. A key step in glucose utilization is the transport of glucose to the cancer cells for supplying their additional energy. The glucose transporter (or GLUT) family is a membrane protein which facilitates the uptake of glucose in most cancer cell types. Given the increased glucose level in cancer cells and the regulatory role of GLUTs in glucose uptake, it is required to combine both experimental and theoretical studies to develop new methods to monitor cell proliferation. Herein, for the first time, a new strategy was proposed to evaluate the cell proliferation of HT-29 based on glucose consumption in the presence of resveratrol (RSV) as an anticancer agent. A hybrid nanocomposite of carbon nanofibers and nitrogen-doped graphene quantum dots was used to design an enzymatic sensor for the selective and sensitive determination of glucose in cancer cells. The results obtained from the voltammetric technique were compared with the conventional colorimetric assay. A good correlation was observed between the proliferation rate and glucose utilization by cancer cells. As it was observed, RSV induces a decrease in glucose consumption, indicating lower glucose uptake efficiency for HT-29 cells. Molecular docking studies reveal that RSV can block the interaction of glucose with the GLUT family. This is one of the possible mechanisms for the decrease of glucose level followed by the reduction of cell proliferation in the presence of RSV. Compared with traditional methods, in vitro electrochemical techniques benefit from simple, nontoxic, sensitive and low-cost detection assays and hence serve as a novel tool to pursue the growth inhibition of cancer cell in response to anti-cancer agents.

Potentiality of PARAFAC approaches for simultaneous determination of N-acetylcysteine and acetaminophen based on the second-order data obtained from differential pulse voltammetry.

N-acetylcysteine (N-AC) has widespread application such as pharmaceutical drug and nutritional supplement. Its adverse effects are rash, urticaria, and itchiness and large doses of N-AC could potentially cause damage to the heart and lungs. Therefore, in this work, a sensitive voltammetric sensor based on a carbon paste electrode modified with silica nano particles (i.e. Mobil Composition of Matter (No. 41) modified with Boron Trifluoride or BF3@MCM-41) with a combination of 4,4'-dihydroxybiphenyl (DHB) (BF3@MCM-41/DHB/CPE) was designed for determination of N-AC. The electrochemical oxidation of N-AC was examined using various techniques such as cyclic voltammetry (CV), chronoamperometry and differential pulse voltammetry (DPV). Under the optimum conditions, some parameters such as electron transfer coefficient (α) and heterogeneous rate constant (ks) were estimated for N-AC. Due to the use of N-AC for the treatment of acetaminophen (AC) overdose, the application of modified electrode was investigated for the simultaneous determination of N-AC and AC in blood serum and tablet samples. Since, the signals of these species overlap and due to the presence of interfering species in blood samples, the simultaneous determination of mentioned species is difficult or impossible. To overcome this challenge, parallel factor analysis (PARAFAC) was used for the analysis of the complex matrices to obtain the spectral profile of each component and interference. To achieve this goal, electrochemical second-order data were generated using a simple change in pulse height of differential pulse voltammetry. The results of the presently proposed strategy for the real samples analysis are similar to those obtained with HPLC. Thus, the proposed method has acceptable performance for simultaneous determination of the two species in real samples.

An in-depth view of potential dual effect of thymol in inhibiting xanthine oxidase activity: Electrochemical measurements in combination with four way PARAFAC analysis and molecular docking insights.

Xanthine oxidase (XO) can catalyze xanthine to uric acid and has also been linked with the extension of some serious diseases such as cancer, gout, diabetes and so on. Thymol is a part of diet in the form of spices. Due to the high antioxidant activity, its inhibitory effect on XO was studied in the present work. XO organized in four redox domains which exhibiting electrochemical signals. Therefore, voltammetric methods can be used to obtain the valuable information about the action mechanism of thymol on XO. However, there are extreme complexities in these biological sample matrices which make the deeper understanding of inhibition mechanism of thymol on XO activity is difficult. Thus, development of electrochemical techniques coupled with the four-way parallel factor analysis (PARAFAC) has provided promising solutions for analyzing of complex matrix. To better explore this inhibitory effect, electrochemical technologies have been used as a complement with ultraviolet and visible (UV-Vis) spectroscopy and molecular docking studies. For the first time, molecular docking studies were used to gain a fundamental understanding to explain how the electron transfer coupling occurs at XO active sites in the presence of thymol. It is in good agreement with the experimental data. These studies reveal that thymol could enter into the catalytic centers of XO. Also, it inhibits the XO activity through the direct binding to flavin adenine dinucleotides (FAD) center. The results display dose-dependent inhibition of XO with thymol. Its inhibitory activity was linked to its antioxidant properties to reduce the formation of free radicals (FRs) and related diseases.