Tag Archives: cytotoxicity

Comparative cytotoxic activity of carboplatin and β-cryptoxanthin in free and liposomal forms against breast cancer cell line

M. W. Shafaa*, N. S. Elkholy

Physics Department, Medical Biophysics Division, Faculty of Science,
Helwan University, Cairo, Egypt;
*e-mail: medhatwi@hotmail.com

Received: 1 June 2020; Accepted: 17 May 2021

The study of the effectiveness of the synthetic and natural anticarcinogenic compounds in liposomal form is urgent for their possible use in therapy. In this work, the alkylating agent carboplatin and the representative of carotenoids β-cryptoxanthin were used. The aim of the research was to study the toxicity of these compounds in free and liposomal forms against breast cancer MCF-7 cell line. According to DSC and FTIR data, when carboplatin or β-cryptoxanthin were added to liposomal bilayers, a single peak was observed indicating their mutual mixing. Integration of  β-cryptoxanthin into bilayer was found to be more proper for the creation of PE acyl chains ordered and cooperative state. It was found that MCF-7 cells sensitivity was much higher to the free β-cryptoxanthin than to the free carboplatin with IC50 42 and 235 μg/ml, respectively. The IC50 values for β-cryptoxanthin loaded into liposomes and for free carboplatin were similar. At the same time, no cytotoxic effect of carboplatin-loaded liposomes was observed. The data obtained allow proposing a possible antitumor treatment regimen where carboplatin is replaced by free β-cryptoxanthin or its liposomal form to increase the effectiveness of breast cancer therapy.

Evaluation of metallothioneins, oxidative stress and signs of cytotoxicity in young obese women

H. I. Falfushynska, O. I. Horyn, V. V. Khoma, G. V. Tereshchuk,
D. V. Osadchuk, N. I. Rusnak, O. B. Stoliar

Ternopil Volodymyr Hnatiuk National Pedagogical University, Ukraine;
e-mail: falfushynska@tnpu.edu.ua

Obesity is rapidly increasing all over the world and pretends to be the global medical and social problem. Thus, the understanding of early signs of obesity and suitable biomarkers is urgently needed for developing an adequate strategy of the obesity prevention and a decrease in its growth rate. The parameters of the lipids’ metabolism and oxidative stress, metallothioneins and signs of cytotoxicity have been investigated in blood samples of young obese women (O-group, 32 < Body Mass Index (BMI) < 37). With regard to persons of O-group they had higher catalase activity (by 435%), level of reactive oxygen species (by 129%), level of oxidised glutathione (by 55%), lipid peroxidation (by 26%) and protein carbonyls (by 345%) in the blood, when compared with control. The obesity was accompanied by an increase in concentration of metallothioneins which have a partial tread effect on radical processes and reduce manifestations of oxidative damage to biomolecules in obese patients. The obese women had the signs of cytotoxicity as higher lactate dehydrogenase activity (by 387%) and DNA fragmentation (by 42%). The principal component analysis revealed the set of biological traits which describes the obesity progress and it included metallothioneins, parameters of oxidative stress, cytotoxicity, BMI and a concentration of low density lipoproteins and total cholesterol. The BMI was in a good correlation with parameters of the lipid metabolism, oxidative injury and cytotoxicity (r > |0.73|, P < 0.001).

Application of calixarenes for DNA transfection in cells

R. V. Rodik

Institute of Organic Chemistry, National Academy of Sciences of Ukraine, Kyiv ,
e-mail: dmso@ukr.net

First results of non-ionic and poly-cationic calixarenes utilization for gene transfection are presented and analyzed in this survey. State of the art in the field of scientific searching for new non-viral vectors are shown in the general form. The prospects of supramolecular concept in design agents for transfection are demonstrated. Some relationships between calixarene architecture and calixarene ability to promote gene transfection are revealed, namely: formation of supramolecular self-assembled aggregates at water media facilitates hierarchical formation of complexes with DNA molecules. Latter particles will effectively transfect genes if they are nano-sized and positively-charged.

Computer prediction of biological activity of dimethyl-N-(benzoyl)amidophosphate and dimethyl-N-(phenylsulfonyl)amidophosphate, evaluation of their cytotoxic activity against leukemia cells in vitro

I. I. Grynyuk, S. V. Prylutska, N. S. Kariaka, T. Yu. Sliva,
O. V. Moroz, D. V. Franskevych, V. M. Amirkhanov,
O. P. Matyshevska, M. S. Slobodyanik

Taras Shevchenko National University of Kyiv, Ukraine;
e-mail: igrynyuk@yahoo.com

Structural analogues of β-diketones – dimethyl-N-(benzoyl)amidophosphate (HCP) and dimethyl-N-(phenylsulfonyl)amidophosphate (HSP) were synthesized and identified by the methods of IR, 1H and 31P NMR spectroscopy. Screening of biological activity and calculation of physicochemical parameters of HCP and HSP compounds were done with the use of PASS and ACD/Labs computer programs. A wide range of biological activity of synthesized compounds, antitumor activity in particular, has been found. Calculations of the bioavailability criteria indicate that the investigated compounds have no deviations from Lipinski’s rules. HCP compound is characterized by a high lipophilicity at physiological pH as compared to HSP. It was found that cytotoxic effect of the studied compounds on the leukemiс L1210 cells was of time- and dose-dependent character. HCP is characterized by more pronounced and early cytotoxic effects as compared to HSP. It was shown that 2.5 mM HCP increased ROS production 3 times in the early period of incubation, and decreased cell viability by 40% after 48 h, and by 66% – after 72 h. Based on the computer calculation and undertaken research, HCP was selected for target chemical modifications and enhancement of its antitumor effect.

Trace elements storage peculiarities and metallothionein content in human thyroid gland under iodine deficiency euthyroid nodular goiter

H. I. Falfushynska1,2, L. L. Gnatyshyna1, O. Osadchuk2, V. O. Shidlovski2, О. B. Stoliar1

1Ternopil Volodymyr Hnatiuk National Pedagogical University, Ukraine;
2I.Ya. Horbachevski Ternopil State Medical University, Ukraine;
e-mail: halynka.f@gmail.com

Accumulation of iodine and copper in the node, paranodular and contralateral (not affected tissue by node) tissues of thyroid gland in relation to the level of metal-binding proteins, potential antioxidants and oxidative changes in tissue was investigated. To assess the severity of the pathological process the molecular markers of cytotoxicity were used. The reduction of total iodine (by 19.5%), increase of inorganic iodine fraction (by 82.4%) and total copper content (twice) in paranodular and nodular tissues compared with contrlateral part have been established. Excess of copper in goitrous-changes tissue was partially accumulated in the metallothioneins. The level of metal-binding form of metallothioneins and reserve of free thiols of these proteins was higher two-three times and lower content of reduced glutathione in node-affected tissue compared to the contralateral part. Signs of cytotoxicity among them: higher cathepsine D free activity (up to 84.6% and 134.4% in paranodular tissue and node respectively) and higher level of DNA strand breaks in the node (up to 22.6%) were observed. In paranodular tissue the range of indices variability compared with parenchyma of contralateral part is shorter than in the node. Thus, under low level of iodine organification and high copper level in goitrous-modified tissue of thyroid gland metallothionein may provide a partial compensatory effect on prooxidative processes.