Journal of Electroanalytical Chemistry, volume 921, pages 116663

Electrochemical characterization of shikonin and in-situ evaluation of interaction with DNA

Ricardo J B Leote 1, 2
Caroline G Sanz 2
Victor C Diculescu 2
1
 
Faculty of Physics, University of Bucharest, Atomistilor 405, 077125 Măgurele, Romania
2
 
National Institute of Materials Physics, Str. Atomistilor 405A, 077125, Măgurele, Romania
Publication typeJournal Article
Publication date2022-09-01
scimago Q1
wos Q2
SJR0.755
CiteScore7.8
Impact factor4.1
ISSN15726657, 18732569
General Chemical Engineering
Analytical Chemistry
Electrochemistry
Abstract
• Shikonin, a natural compound with pharmaceutical properties; • Shikonin reduction results in semiquinone radical and superoxide; • Shikonin induces DNA conformational modification. • In-situ shikonin reduction leads to occurrence 8-oxo-guanine. • Shikonin-DNA interaction mechanism proposed. Shikonin, a natural compound with pharmaceutical properties, has attracted interest due to its anti-oxidant properties, potential anti-cancer activity and activity over several biological pathways, such as dsDNA transcription/replication of cancer cells and inhibition of pyruvate kinase M2. The electrochemical behavior of shikonin in aqueous media was investigated at glassy carbon electrodes by cyclic and differential pulse voltammetry. The reduction involves the quinone moiety and formation of a semiquinone intermediate. In the absence of dissolved oxygen, the reduction is reversible while in normal atmosphere leads to formation of superoxide cation. The oxidation occurs at the dihydroxy moiety and reversibility was only observed in acid electrolytes. A redox mechanism was proposed. The interaction between shikonin and ds DNA was evaluated in incubated solutions and in situ with the dsDNA-electrochemical biosensor. The mechanism of interaction is time-dependent and follows an initial binding step at the grooves of the double strand leading to conformational modifications recognized through the variation of guanine and adenine oxidation peaks. The in-situ electrochemical production of the semiquinone intermediate leads to a preferential interaction with guanine residues, promoting their oxidation and consequently occurrence 8-oxo-guanine. An interaction mechanism was proposed.
Sanz C.G., Buoro R.M., Bacil R.P., da Silva I.S., Rendelucci A.D., Costa F.P., Serrano S.H.
2023-01-01 citations by CoLab: 3 Abstract  
DNA analysis usually requires enhanced sensitivity techniques to detect even the slightest molecular alteration. Electrochemical methods provide versatile, accessible and powerful tools with enhanced sensitivity, selectivity and ease of manipulation, in which sensors with several architectural possibilities can be developed towards biochemical, biomedical and environmental assays. DNA-based sensors and biosensors can be applied to the evaluation of DNA-drug interactions, in a non-specific signal transducing mechanism, and also in the detection of specific genetic sequences of cancer biomarkers, pathogens, as well as in food analysis. Here, the development, transducing mechanism, and applications of DNA-based sensors and biosensors are discussed.
Bacil R.P., Garcia P.H., Serrano S.H.
2022-03-01 citations by CoLab: 19 Abstract  
• Epinephrine oxidizes in an EECEE mechanism instead of ECE. • The oxidations processes present potential inversions. • A more detailed EECEE mechanism to epinephrine oxidation is proposed. • The cyclization rate constants were experimentally obtained ( k f = 18.9 s −1 ) and validated by digital simulations. • The apparent Gibbs energies were obtained as a function of pH. The classic epinephrine’s ECE mechanism was revisited. The data obtained suggest that its mechanism is a multi-step irreversible electron transfer with a very fast intramolecular cyclization, an EECEE with a potential inversion, instead of a couple of two-electron processes in a single-step transfer. Moreover, the electrochemical and chemical steps are pH dependent. This conclusion is based on the combination of experimental data with Tafel analysis, digital simulations, and Gibbs energy and Randles-Sevcik predictions. A more detailed electrochemical mechanism was thus proposed to epinephrine’s electrooxidation.
Dembic Z.
Molecules scimago Q1 wos Q2 Open Access
2020-12-07 citations by CoLab: 49 PDF Abstract  
Through novel methodologies, including both basic and clinical research, progress has been made in the therapy of solid cancer. Recent innovations in anticancer therapies, including immune checkpoint inhibitor biologics, therapeutic vaccines, small drugs, and CAR-T cell injections, mark a new epoch in cancer research, already known for faster (epi-)genomics, transcriptomics, and proteomics. As the long-sought after personalization of cancer therapies comes to fruition, the need to evaluate all current therapeutic possibilities and select the best for each patient is of paramount importance. This is a novel task for medical care that deserves prominence in therapeutic considerations in the future. This is because cancer is a complex genetic disease. In its deadly form, metastatic cancer, it includes altered genes (and their regulators) that encode ten hallmarks of cancer-independent growth, dodging apoptosis, immortalization, multidrug resistance, neovascularization, invasiveness, genome instability, inflammation, deregulation of metabolism, and avoidance of destruction by the immune system. These factors have been known targets for many anticancer drugs and treatments, and their modulation is a therapeutic goal, with the hope of rendering solid cancer a chronic rather than deadly disease. In this article, the current therapeutic arsenal against cancers is reviewed with a focus on immunotherapies.
Khan T., Ali M., Khan A., Nisar P., Jan S.A., Afridi S., Shinwari Z.K.
Biomolecules scimago Q1 wos Q1 Open Access
2019-12-27 citations by CoLab: 216 PDF Abstract  
The rising burden of cancer worldwide calls for an alternative treatment solution. Herbal medicine provides a very feasible alternative to western medicine against cancer. This article reviews the selected plant species with active phytochemicals, the animal models used for these studies, and their regulatory aspects. This study is based on a meticulous literature review conducted through the search of relevant keywords in databases, Web of Science, Scopus, PubMed, and Google Scholar. Twenty plants were selected based on defined selection criteria for their potent anticancer compounds. The detailed analysis of the research studies revealed that plants play an indispensable role in fighting different cancers such as breast, stomach, oral, colon, lung, hepatic, cervical, and blood cancer cell lines. The in vitro studies showed cancer cell inhibition through DNA damage and activation of apoptosis-inducing enzymes by the secondary metabolites in the plant extracts. Studies that reported in vivo activities of these plants showed remarkable results in the inhibition of cancer in animal models. Further studies should be performed on exploring more plants, their active compounds, and the mechanism of anticancer actions for use as standard herbal medicine.
Sanz C.G., Serrano S.H., Brett C.M.
2019-07-01 citations by CoLab: 11 Abstract  
The electrochemical behaviour of cefadroxil, a first-generation β-lactam antibiotic, was studied at glassy carbon electrodes in aqueous media over a wide range of pH. The first oxidation process is of the phenol moiety and follows an ECE mechanism, generating catechol and resorcinol derivatives as sub-products, which are then reduced and oxidized in subsequent cycles. The sulphur heteroatom present in the cyclic structure close to the β-lactam moiety is oxidized in two steps generating sulphoxide and sulphone. This process was identified from direct comparison with amoxicillin, which has a similar molecular structure, although they belong to different classes of β-lactam antibiotics. For amoxicillin, oxidation of the sulphur heteroatom occurred at more positive potentials, most likely due to structural difficulties in stabilizing the charged oxidized species. Formation of a complex between copper (II) and each of the antibiotics was studied by cyclic voltammetry. Finally, determination of cefadroxil in commercial samples was successfully carried out.
Promraksa B., Phetcharaburanin J., Namwat N., Techasen A., Boonsiri P., Loilome W.
PLoS ONE scimago Q1 wos Q1 Open Access
2019-05-23 citations by CoLab: 22 PDF Abstract  
Although cholangiocarcinoma (CCA) has a low incidence globally, this is extremely high in Northeast Thailand. The lack of both early detection measures and effective therapeutic drugs is the major problem for the poor prognosis of CCA patients. Based on regional knowledge, it would be advantageous to search for effective natural phyto-products for the treatment of CCA. Cardiospermum halicacabum L., Gomphrena celosioides Mart. and Scoparia dulcis L., very well-known medicinal herbs in Asian countries, were selected for the investigation of inhibitory effects on CCA cells. Of the three different ethanolic extracts, S. dulcis L extract showed most inhibitory effects on cell growth of CCA cell lines KKU-100 and KKU-213, at percentages of 56.06 and 74.76, respectively, compared to the untreated group after treatment with 250 μg/mL of extracts for 72 hrs. At 400 and 500 μg/mL of the extracts, the inhibitory effect of KKU-213 was indicated by a significant increase in the BAX/Bcl-2 ratio and cell membrane permeability. Moreover, metabolic profiling-based screening employed in the current study revealed a significant positive association between the lignin compound and a decrease in CCA cell viability. Our study suggests, for the first time, that ESD has the ability to inhibit CCA cell growth through the induction of apoptosis.
Figat R., Zgadzaj A., Geschke S., Sieczka P., Pietrosiuk A., Sommer S., Skrzypczak A.
Drug and Chemical Toxicology scimago Q2 wos Q3
2018-12-21 citations by CoLab: 15
Ferapontova E.E.
2018-06-12 citations by CoLab: 145 Abstract  
Sensitive, specific, and fast analysis of nucleic acids (NAs) is strongly needed in medicine, environmental science, biodefence, and agriculture for the study of bacterial contamination of food and beverages and genetically modified organisms. Electrochemistry offers accurate, simple, inexpensive, and robust tools for the development of such analytical platforms that can successfully compete with other approaches for NA detection. Here, electrode reactions of DNA, basic principles of electrochemical NA analysis, and their relevance for practical applications are reviewed and critically discussed.
Zhou Z., Lu B., Wang C., Wang Z., Luo T., Piao M., Meng F., Chi G., Luo Y., Ge P.
Cancer Letters scimago Q1 wos Q1
2017-04-01 citations by CoLab: 50 Abstract  
Shikonin has been reported to induce glioma cell death via necroptosis, a type of programmed necrosis primarily mediated by RIP1 and RIP3. Although RIP1 and RIP3 are found to regulate some features of necrosis such as energy depletion and cellular membrane disruption, it remains unclear whether RIP1 and RIP3 could modulate DNA double strand breaks (DSBs), which is a crucial event leading to chromatinolysis. In this study, we used glioma cell lines and mice model of xenograft glioma to investigate the roles of RIP1 and RIP3 in shikonin-induced DNA DSBs. We found that shikonin induced upregulation of RIP1 and RIP3, necrosome formation and DNA DSBs in vitro and in vivo. In vitro investigation showed that the DNA DSBs and the reduction of cellular viabilities induced by shikonin were both prevented when RIP1 or RIP3 was pharmacologically inhibited by specific inhibitor or genetically knocked down with siRNA. Then, we proved that suppression of intracellular ROS with antioxidant NAC inhibited DNA DSBs caused by either hydrogen peroxide or shikonin, suggesting that ROS played a crucial role in regulation of DNA DSBs of glioma cells induced by shikonin. Further, we found that RIP1 and RIP3 regulated shikonin-induced overproduction of ROS via causing excessive generation of mitochondrial superoxide and depletion of GSH, indicating that ROS was the downstream signal of RIP1 and RIP3. Taken together, we demonstrated that RIP1 and RIP3 contributed to shikonin-induced DNA DSBs in glioma cells via increase of intracellular ROS levels.
Liang W., Cai A., Chen G., Xi H., Wu X., Cui J., Zhang K., Zhao X., Yu J., Wei B., Chen L.
Scientific Reports scimago Q1 wos Q1 Open Access
2016-12-01 citations by CoLab: 69 PDF Abstract  
The prognosis of gastric cancer remains poor due to clinical drug resistance. Novel drugs are urgently needed. Shikonin (SHK), a natural naphthoquinone, has been reported to trigger cell death and overcome drug resistance in anti-tumour therapy. In this study, we investigated the effectiveness and molecular mechanisms of SHK in treatment with gastric cancer. In vitro, SHK suppresses proliferation and triggers cell death of gastric cancer cells but leads minor damage to gastric epithelial cells. SHK induces the generation of intracellular reactive oxygen species (ROS), depolarizes the mitochondrial membrane potential (MMP) and ultimately triggers mitochondria-mediated apoptosis. We confirmed that SHK induces apoptosis of gastric cancer cells not only in a caspase-dependent manner which releases Cytochrome C and triggers the caspase cascade, but also in a caspase-independent manner which mediates the nuclear translocation of apoptosis-inducing factor and Endonuclease G. Furthermore, we demonstrated that SHK enhanced the chemotherapeutic sensitivity of 5-fluorouracil and oxaliplatin in vitro and in vivo. Taken together, our data show that SHK may be a novel therapeutic agent in the clinical treatment of gastric cancer.
Maldonado T., Martínez-González E., Frontana C.
Electroanalysis scimago Q2 wos Q3
2016-07-19 citations by CoLab: 7 Abstract  
In this work, an electrochemical and spectroelectrochemical ESR study for a series of hydroxyl substituted 1,4-naphthoquinones is presented. Results show that the electrochemical behaviour is dependent on the relative positions of these groups within the molecules. For compounds which have hydroxyl groups at the annellated benzene ring, intramolecular hydrogen bonding (a substituent field effect) determines the energy of reduction of the system. When hydroxyl functions are located at the C-2 or C-3 positions, a selfprotonation process occurs. The electrogenerated dianion or trianion radicals, derived from deprotonated quinones, show that intramolecular hydrogen bonding has a significant effect both in the spin density distribution and in the energy required for the formation of these radical species. The difference observed in the slope for EpIc vs. log v function for 2,3,5,8-tetrahydroxy-1,4-naphthoquinone suggest that, for this compound, the proton transfer step does not occur as a single, but as a two-step sequence, where an hydrogen bonded adduct could be present as a stable intermediate. These processes could help to explain the discrepancies observed earlier performing linear free energy relationships these compounds.
Diculescu V.C., Chiorcea-Paquim A., Oliveira-Brett A.M.
2016-05-01 citations by CoLab: 166 Abstract  
As carrier of genetic information, DNA is one of the most important intracellular targets that undergo modification and damage upon interaction with endogenous and exogenous factors. DNA is an excellent biomaterial for the construction of new devices, in nanotechnology and biosensor technology, for evaluation of DNA interaction with a broad range of chemical compounds and biomolecules, essential from a biological and a medical point of view. This review discusses recent advances on the design and applications of DNA-electrochemical biosensors that use DNA direct electrochemistry as a detection platform. AFM and voltammetric characterization of new bottom up immobilisation procedures of self-assembled nanostructures based on DNA single- and double-stranded, G-quadruplex, and i-motif configurations are presented, relevant for the development of new DNA-electrochemical biosensor devices. The applications of DNA-electrochemical biosensors, for the label-free detection of interactions with proteins, pharmaceutical compounds, metal ions and metal complexes, pollutants, free radicals, and electromagnetic radiation, were revisited.
Diculescu V.C., Oliveira-Brett A.M.
Bioelectrochemistry scimago Q2 wos Q2
2016-02-01 citations by CoLab: 39 Abstract  
Danusertib is a kinase inhibitor and anti-cancer drug. The evaluation of the interaction between danusertib and dsDNA was investigated in bulk solution and using the dsDNA-electrochemical biosensor. The dsDNA-danusertib interaction occurs in two sequential steps. First, danusertib binds electrostatically todsDNA phosphate backbone through the positively charged piperazine moiety. The second step involved the pyrrolo-pyrazolemoiety and led to small morphological modifications in the dsDNA double helix which were electrochemically characterised through the changes of guanine and adenine residue oxidation peaks and confirmed by electrophoretic and spectrophotometric measurements. The nitrenium cation radical product of danusertib amino group oxidation was electrochemically generated in situ on the dsDNA-electrochemical biosensor surface. The danusertib nitrenium cation radical redox metabolite was covalently attached to the C8 of guanine residues preventing their oxidation. An interaction mechanism of dsDNA-danusertib is proposed and the formation of the danusertib redox nitrenium radical metabolite-guanine adduct explained.
Tomé L.I., Marques N.V., Diculescu V.C., Oliveira-Brett A.M.
Analytica Chimica Acta scimago Q1 wos Q1
2015-10-14 citations by CoLab: 16 Abstract  
The interaction of the anticancer monoclonal antibody bevacizumab (BEVA) with double-stranded DNA (dsDNA) was studied by voltammetry and gel-electrophoresis in incubated samples and using the dsDNA-electrochemical biosensor. The voltammetric results revealed a decrease and disappearance of the dsDNA oxidation peaks with increasing incubation time, showing that BEVA binds to the dsDNA but no DNA oxidative damage was detected electrochemically. Non denaturing agarose gel-electrophoresis experiments were in agreement with the voltammetric results showing the formation of compact BEVA-dsDNA adduct. The dsDNA-electrochemical biosensor in incubated solutions showed that BEVA also undergoes structural modification upon binding dsDNA, and BEVA electroactive amino acid residues oxidation peaks were detected.
Eda Satana Kara H.
Bioelectrochemistry scimago Q2 wos Q2
2014-10-01 citations by CoLab: 51 Abstract  
Idarubicin (IDA), 4-demethoxydaunorubicin, is an anthracycline derivative and widely used treatment of leukemia. The electrochemical behavior of IDA was examined at a glassy carbon electrode (GCE) in different aqueous supporting electrolyte using cyclic voltammetry (CV) and differential pulse voltammetry (DPV). The oxidation process of IDA was found to be pH dependent and irreversible proceeding with a transfer of 1 proton and 1 electron under the diffusion controlled mechanism. The electroactive center is the hydroxyl group on the aromatic ring which produces a final quinonic product. The diffusion coefficient of IDA was calculated to be D IDA = 7.47 × 10 − 6 cm 2 s − 1 in pH = 4.3 0.1 M acetate buffer. The interaction of IDA and double stranded deoxyribonucleic acid (ds-DNA) was investigated using electrochemical ds-DNA biosensor and incubation solution by means of DPV. The DNA damage was detected following the changes in the oxidation peaks of guanosine and adenosine residues. The results obtained showed that IDA interacts with DNA which causes the change in the DNA morphological structure. In addition to these polynucleotides, PolyG and PolyA, biosensors were also used to confirm the interaction between ds-DNA and IDA. However, no oxidation peaks of the purine base oxidation products, 8-oxoGua and 2,8-oxoAde, were observed. • Clarify idarubicin electrochemical behavior • Propose an oxidation mechanism for idarubicin • In situ evaluation of idarubicin–DNA interaction
Aseeva N.V., Danilenko N.V., Plotnikov E.V., Korotkova E.I., Lipskikh O.I., Solomonenko A.N., Erkovich A.V., Eskova D.D., Khlebnikov A.I.
2024-11-14 citations by CoLab: 1 PDF Abstract  
This study presents the synthesis of new fluorosulfate derivatives of 1,4-naphthoquinone by the SuFEx reaction. Anticancer properties of obtained compounds were studied on PC-3 (prostate adenocarcinoma), SKOV-3 (ovarian cancer), MCF-7 (breast cancer), and Jurkat cell lines. All the studied compounds showed higher cytotoxic effects than Cisplatin. The DFT method was applied to determine the electronic structure characteristics of 1,4-naphthoquinone derivatives associated with cytotoxicity. A method of determination of 2,3-dichloro-1,4-naphthoquinone (NQ), 3-chloro-2-((4-hydroxyphenylamino)-1,4-naphthoquinone (NQ1), and 4-((3-chloro-1,4-naphthoquinon-2-yl)amino)phenyl fluorosulfate (NQS) in a pharmaceutical substance using an impregnated graphite electrode (IMGE) was developed. The morphology of the IMGE surface was studied using scanning electron microscopy (SEM). The electrochemical behavior of NQ, NQ1, and NQS was studied by cyclic voltammetry (CV) in 0.1 M NaClO4 (96% ethanol solution) at pH 4.0 in a potential range from −1 to +1.2 V. Electrochemical redox mechanisms for the investigated compounds were proposed based on the determining main features of the electrochemical processes. Calibration curves were obtained by linear scan voltammetry in the first derivative mode (LSVFD) with the detection limit (LOD) 7.2 × 10−6 mol·L−1 for NQ, 8 × 10−7 mol·L−1 for NQ1, and 8.6 × 10−8 mol·L−1 for NQS, respectively.
Beregoi M., Oprea D., Bunea M.C., Enculescu M., Enache T.A.
Microchimica Acta scimago Q1 wos Q1
2024-06-29 citations by CoLab: 0 Abstract  
AbstractA novel scaffold for in situ electrochemical detection of cell biomarkers was developed using electrospun nanofibers and commercial adhesive polymeric membranes. The electrochemical sensing of cell biomarkers requires the cultivation of the cells on/near the (bio)sensor surface in a manner to preserve an appropriate electroactive available surface and to avoid the surface passivation and sensor damage. This can be achieved by employing biocompatible nanofiber meshes that allow the cells to have a normal behavior and do not alter the electrochemical detection. For a better mechanical stability and ease of handling, nylon 6/6 nanofibers were collected on commercial polymeric membranes, at an optimal fiber density, obtaining a double-layered platform. To demonstrate the functionality of the fabricated scaffold, the screening of cellular stress has been achieved integrating melanoma B16-F10 cells and the (bio)sensor components on the transducer whereas the melanin exocytosis was successfully quantified using a commercial electrode. Either directly on the surface of the (bio)sensor or spatially detached from it, the integration of cell cultures in biosensing platforms based on electrospun nanofibers represents a powerful bioanalytical tool able to provide real-time information about the biomarker release, enzyme activity or inhibition, and monitoring of various cellular events. Graphical Abstract
Mehmet A., Firat A., Abdulkadir L.
Talanta scimago Q1 wos Q1
2023-12-01 citations by CoLab: 14 Abstract  
A sensitive, simple, fast electrochemical biosensor for the DNA interaction of bevacizumab (BEVA), which is used as a targeted drug in cancer treatment, was developed using the differential pulse voltammetry (DPV) technique with pencil graphite electrode (PGE). In the work, PGE was electrochemically activated in a supporting electrolyte medium of +1.4 V/60 s (PBS pH 3.0). Surface characterization of PGE was carried out by SEM, EDX, EIS, and CV techniques. Determination and electrochemical properties of BEVA were examined with CV and DPV techniques. BEVA gave a distinct analytical signal on the PGE surface at a potential of +0.90 V (vs. Ag/AgCl). In the procedure proposed in this study, BEVA gave a linear response on PGE in PBS (pH 3.0 containing 0.02 M NaCl) (0.1 mg mL−1 – 0.7 mg mL−1) with LOD and LOQ values of 0.026 mg mL−1 and 0.086 μg mL−1, respectively. BEVA was reacted with 20 μg mL−1 DNA in PBS for 150 s and analytical peak signals for adenine and guanine bases were evaluated. The interaction between BEVA-DNA was supported by UV–Vis. Absorption spectrometry and the binding constant was determined as 7.3 × 104.

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