Examination of Prooxidative Activity of Red Wine in Melanoma Cells

Melanoma is responsible for 75% of all deaths from skin cancer. Its lethality arises from its rapid progression, easy metastasis and drug-resistance as well. Red wine is a natural product rich in polyphenolic compounds with potent anticancer activities. It seems that in cancer cells these compounds behave as prooxidants initiating reactive oxygen species mediated cellular DNA breakage and consequent cell death. The aim of this study was to investigate prooxidative activity of red wine samples (Merlot variety, commercial as well as VCR1 and VCR101 clonal wines) in melanoma A375 cells, through measuring the relationship of reduced and oxidized form of glutathione (GSH/GSSG) and comparison with the GSH/GSSG ratio in control (untreated melanoma cells). The data obtained showed that tested red wine samples decrease GSH/GSSG ratio in A375 cells compared to control (4.6 ± 0), with the largest decrease noticed in treatment with VCR101 wine (0.66 ± 0.05)

Citotoksično dejstvo crvenog vina na tumorske ćelije u in vitro uslovima

Benefitni efekat crvenog vina na zdravlje ljudi od davnina je poznat. Među alkoholnim pićima crveno vino pokazuje najjači efekat protiv pojave oboljenja povezanih sa oksidativnim stresom, kao što su kardiovaskularna, neurodegenerativna oboljenja, dijabetes i kancer.1 U okviru ove studije ispitan je citotoksični efekat crvenog vina sorte merlo (komercijalno dostupno vino i vina dobijena od klonova VCR1 i VCR101) poreklom iz Crne Gore, berba 2011, u odnosu na ćelijsku liniju kancera pankreasa (PANC-1) i ćelijsku liniju melanoma (A375). Citotoksični efekat vina je određen SRB metodom kroz praćenje ćelijskog preživljavanja kancerskih ćelija 48 sati nakon tretmana sa tri različita zapreminska procenta analiziranih vina (5, 10 i 20%). Dobijeni rezultati su pokazali citotoksični efekat svih analiziranih vina na obe ćelijske linije. Ćelijsko preživljavanje nakon tretmana vinima se kretalo od 36 do 64%. Citotoksični efekat svih vina u odnosu na A375 ćelije je bio veći nego na PANC-1 ćelijsku liniju, što je od posebnog značaja ako se uzme u obzir rezistentnost melanomskih ćelija na postojeće terapeutske tretmane. Takođe, klonska sortna vina su pokazala veći citotoksični efekat na A375 ćelijsku liniju od komercijalno dostupnog vina. Dobijeni rezultati su ukazali da umereno konzumiranje crvenog vina sorte merlo sa specifičnim geografskim poreklom predstavlja dobar izvor bioaktivnih komponenata sa pozitivnim biološkim efektom, što je od posebne važnosti za klonska sortna vina.3. kongres biologa Srbije : osnovna i primenjena istraživanja, metodika nastave, 21-25. septembar 2022., Zlatibor, Srbij

The metal-doped TiO2 nanoparticles as photosensitizers in photodynamic therapy of melanoma

Melanoma is one of the most severe life-threatening diseases with a highly aggressive biologic behavior. Despite all improvements in diagnosis and therapy, most deaths from melanoma are due to metastases that are resistant to conventional treatment modalities [1]. Photodynamic therapy (PDT) is a relatively new treatment modality that has been successfully applied to many diseases and disorders, including skin cancers. PDT uses a combination of a light-sensitive substance (known as a photosensitizer, PS) and light of an appropriate wavelength. After the activation by light, PS reacts with molecular oxygen producing reactive oxygen species (ROS) and radicals, which cause intracellular biochemical changes leading to cell death [2]. Titanium dioxide nanoparticles (TiO2 NPs) are commonly used PSs in PDT [3], but they absorb strongly in the UV light range. Doping TiO2 NPs with ions leads to an increase in the absorption edge wavelength and a decrease in the bandgap energy, enabling the application of a less damaging visible light for the NP activation. However, to our best knowledge, metal-doped TiO2 has not been extensively tested as PSs. This study aimed to investigate the effects of colloidal TiO2 NPs and prolate nanospheroids (PNSs) doped with Cu and Ni on melanoma cell lines (A375) in the dark and under blue light irradiation. In general, doped TiO2 NPs show higher photocatalytic activity than undoped analog. Among them, the best photocatalytic activity showed TiO2 NPs doped with Cu [4]. However, colloidal TiO2 NPs have a diameter of 5 nm, whereas PNSs are around 20 nm long. Therefore, the cytotoxicity of cells was dependent on the dopant and the size of NPs. Still, in all cases, it is augmented by the light illumination, implying the potential use of doped TiO2 NPs with Cu and Ni as a light-sensitive drug in PDT of melanoma. In summary, our results can contribute to the development of more efficient skin cancer treatment modalities.VIII International School and Conference on Photonics and HEMMAGINERO workshop : PHOTONICA2021 : book of abstracts; August 23-27, 2021; Belgrad

Phenolic Composition and Cytotoxic Activity of Red Wine

Positive effects of moderate wine consumption in individuals with cardiovascular disease, hypertension, diabetes, and cancers have been shown in numerous epidemiological and clinical studies. This research examined the phenolic content of commercial and two clonal Merlot wines as well as their biological potential. The obtained results indicated that all analyzed samples were a good source of phenolic compounds. Cytotoxicity assay on melanoma (A375) and cervical (HeLa) cancer cell lines have shown that all analyzed wines inhibited the growth of human cancer cells in vitro with differing susceptibility among tested cell lines. Clonal wines in the volume ratio of 10 and 20% showed to be more efficient anti-proliferative agents than commercial wine regarding the A375 cells. This could be connected with higher total phenolic content in clonal wines. The effect of all analyzed samples on the A375 cells was greater compared to HeLa cell line.XVI International Conference on Fundamental and Applied Aspects of Physical Chemistry, September 26-30, Belgrad

Light controlled metallo-drug delivery system based on the TiO(2-)nanoparticles and Ru-complex

We studied the colloidal TiO2 nanoparticles as a carrier for controlled delivery of the ruthenium complex to the melanoma cell line. The system demonstrated slower complex release upon visible and increased release rate upon UV light illumination. Accordingly, the light-dependent cytotoxicity of the system was demonstrated on amelanotic melanoma cancer line. The cell death is enhanced by UV and reduced by red light in the presence of investigated nanocomposite system. Both components of the system may act as photosensitizers, by generating reactive oxygen species, which promote cell death. Thus, the system might act dually, as photodynamic therapeutic agent and as the light tunable system for metallo-drug delivery and it might be of interest for development of new more efficient drug delivery approaches by using a light as external stimulus. (C) 2017 Elsevier B.V. All rights reserved

TiO2-Based Nanocomposite System as Light-Controlled Metallo-drug Delivery System

RIAO-OPTILAS 2016 : IX Iberoamerican Meeting on Optics and XII Iberoamerican Meeting on Optics, Lasers and Applications : November 21-25, 2016, Pucon, Chil

Cytotoxic activity and influence on acetylcholinesterase of series dinuclear platinum(II) complexes with aromatic nitrogen-containing heterocyclic bridging ligands: Insights in the mechanisms of action

Herein, the stability, lipophilicity, in vitro cytotoxicity, and influence on acetylcholinesterase of five dinuclear platinum(II) complexes with the general formula [{Pt(en)Cl}2(μ-L)]2+ (L is a different aromatic nitrogen-containing heterocyclic bridging ligands pyrazine (pz, Pt1), pyridazine (pydz, Pt2), quinoxaline (qx, Pt3), phthalazine (phtz, Pt4) and quinazoline (qz, Pt5), while en is bidentate coordinated ethylenediamine) were evaluated. The most active analyzed platinum complexes induced time-dependent growth inhibition of A375, HeLa, PANC-1, and MRC-5 cells. The best efficiency was achieved on HeLa and PANC-1 cells for Pt1, Pt2, and Pt3 at the highest concentration, while Pt1 was significantly more potent than cisplatin at a lower concentration. Additionally, a lower effect on normal cells was observed compared to cisplatin, which may indicate potentially fewer side effects of these complexes. Selected complexes induce reactive oxygen species and apoptosis on tumor cell lines. The most potent reversible acetylcholinesterase (AChE) inhibitors were Pt2, Pt4, and Pt5. Pt1 showed similar inhibitory potential toward AChE as cisplatin, but a different type of inhibition, which could contribute to lower neurotoxicity. Docking studies revealed that Pt2 and Pt4 were bound to the active gorge above the catalytic triad. In contrast, the other complexes were bound to the edge of the active gorge without impeding the approach to the catalytic triad. According to this, Pt1 represents a promising compound with potent anticancer properties, high selectivity, and low neurotoxicity

Controlled killing of human cervical cancer cells by combined action of blue light and C-doped TiO2 nanoparticles

In this study, C-doped TiO2 nanoparticles (C-TiO2) were prepared and tested as a photosensitizer for visible-light-driven photodynamic therapy against cervical cancer cells (HeLa). X-ray diffraction and Transmission Electron Microscopy confirmed the anatase form of nanoparticles, spherical shape, and size distribution from 5 to 15 nm. Ultraviolet–visible light spectroscopy showed that C doping of TiO2 enhances the optical absorption in the visible light range caused by a bandgap narrowing. The photo-cytotoxic activity of C-TiO2 was investigated in vitro against HeLa cells. The lack of dark cytotoxicity indicates good biocompatibility of C-TiO2. In contrast, a combination with blue light significantly reduced the survival of HeLa cells: illumination only decreased cell viability by 30% (15 min of illumination, 120 µW power), and 60% when HeLa cells were preincubated with C-TiO2. We have also confirmed blue light-induced C-TiO2-catalyzed generation of reactive oxygen species in vitro and intracellularly. Oxidative stress triggered by C-TiO2/blue light was the leading cause of HeLa cell death. Fluorescent labeling of treated HeLa cells showed distinct morphological changes after the C-TiO2/blue light treatment. Unlike blue light illumination, which caused the appearance of large necrotic cells with deformed nuclei, cytoplasm swelling, and membrane blebbing, a combination of C-TiO2/blue light leads to controlled cell death, thus providing a better outcome of local anticancer therapy