Tag Archives: breast cancer cells

Cytotoxicity of dextran-graft-polyacrylamide/zinc oxide nanoparticles against doxorubicin-resistant breast cancer cells

P. A. Virych1, V. A. Chumachenko2, P. A. Virych2,
V. O. Pavlenko2, N. V. Kutsevol2

1Laboratory of Mechanisms of Drug Resistance, R.E. Kavetsky Institute for Experimental Pathology,
Oncology and Radiobiology, National Academy of Sciences of Ukraine, Kyiv;
2Chemistry Department, Taras Shevchenko National University of Kyiv, Kyiv, Ukraine;
*e-mail: anabenasp@gmail.com

Received: 24 August 2023; Revised: 08 October 2023;
Accepted: 01 December 2023; Available on-line: 18 December 2023

The toxicity of drugs for chemotherapy and cell resistance to their action are the main obstacles in anticancer therapy. Advances in nanotechnology may offer an alternative to traditional methods of anticancer therapy and overcoming drug resistance. The study was carried out on doxorubicin-resistant MCF-7/Dox breast cancer cells and BALB/3T3 clone A31 as a model of normal fibroblasts with the use of Dextran-graft-polyacrylamide/zinc oxide (D-PAA/ZnO) nanoparticles. Cytomorphological analysis was carried out after cells staining with acridine orange. Immunocytochemical study of Ki-67, p53, Bcl-2, Bax, E-cadherin, N-cadherin, СD44 expression was done. Cytotoxicity of D-PAA/ZnO nanoparticles (EC50 = 2.2 mM) against MCF-7/Dox cancer cells but not against normal fibroblasts was demonstrated. The increased expression of proapoptotic proteins, E-cadherin, CD44 and decreased expression of proliferation-associated marker Ki-67 in cancer cells treated with D-PAA/ZnO was revealed. Cytotoxicity of D-PAA/ZnO NPs against MCF-7/Dox cancer cells can be potentially used for elaboration of new approaches to cancer treatment.

Cytotoxic effect of Ziziphus Spina-Christi extract alone and in combination with doxorubicin on breast cancer cells

E. S. El-Shafey, E. S. Elsherbiny*

Biochemistry Department, Faculty of Science, Damietta University, Damietta, Egypt;
*e-mail: eslamsamy1@yahoo.com

Received: 17 July 2023; Revised: 23 October 2023;
Accepted: 01 December 2023; Available on-line: 18 December 2023

Ziziphus Spina-Christi (L.) (ZSC) is a traditional Arabian medicinal plant used to treat inflammatory symptoms, swellings and pain since long. Triple negative breast cancer (TNBC) is a form of cancer with a poor prognosis owing to the paucity of therapy alternatives. Two of the most critical pathways of TNBC development are Wnt/β-catenin signaling and autophagy. In the present study, we intended to identify the possible mechanisms of the cytotoxic effects mediated by ZSC extract on MDA-MB-231 breast cancer cells and to improve the efficacy of DOX in combination with ZSC. The MTT test was used to estimate cell viability and IC50 values. Apoptosis was detected using AnnexinV-FITC detection kit. ELISA was used to measure caspase-3 levels. Cell cycle and the level of autophagosome marker LC3-II were analysed using flow cytometry. Acidic vesicular organelle (AVOs) formation was observed by fluorescence microscopy. Real-time PCR was used to monitor changes in gene expression of β-catenin and autophagic adapter NBR1. It was shown that ZSC treatment dose-dependently inhibited MDA-MB-231 cell viability and induced apoptosis with accompanying elevation of caspase-3 level. Besides ZSC caused a significant elevation in LC3II level and downregulation of NBR1 gene expression with subsequent downregulation of β-catenin gene expression, indicating the inhibition of the oncogenic Wnt pathway. ZSC and DOX combination had synergistic cytotoxic effect by more effective suppression of Wnt pathway and induction of apoptosis and autosis.

Effect of a novel thiazole derivative and its complex with a polymeric carrier on stability of DNA in human breast cancer cells

N. S. Finiuk1,2, O. Yu. Klyuchivska1, I. I. Ivasechko1,
N. E. Mitina3, Yu. V. Ostapiuk2, M. D. Obushak2,
O. S. Zaichenko3, A. M. Babsky2, R. S. Stoika1,2*

1Institute of Cell Biology, NAS of Ukraine, Lviv, Ukraine;
2Ivan Franko National University of Lviv, Lviv, Ukraine;
3Lviv Polytechnic National University, Lviv, Ukraine;
*e-mail: stoika.rostyslav@gmail.com

Received: 26 January 2021; Accepted: 2021

Thiazole derivatives are perspective antitumor compounds characterized by a broad range of bioactivity, while polymeric carriers are widely used to enhance the efficiency of biological action of drugs, improve their biocompatibility and water solubility. Previously, we identified that the thiazole-based derivative BF1 (N-(5-benzyl-1,3-thiazol-2-yl)-3,5-dimethyl-1-benzofuran-2-carboxamide) possessed differential toxicity towards targeted tumor cell lines. The aim of the present work was to investigate the action in vitro of BF1 and its complex with the polymeric carrier (PC) poly(PEGMA-co-DMM) (BF1-РС complex) towards human breast adenocarcinoma cells of the MDA-MB-231 and MCF-7 lines. DNA comet analysis, diphenylamine DNA fragmentation assay, gel retardation assay of plasmid DNA, DNA intercalation assay using methyl green dye and fluorescent microscopy were used to study the effects of BF1 on DNA stability in breast cancer cells. The ІС50 of cytotoxic action towards MDA-MB-231 cells was 26.5 ± 2.9 µМ for BF1, while the ІС50 for the BF1-PC complex was 6.9 ± 0.4 µМ, and the PC demonstrated low toxicity (ІС50 ˃ 50 µМ). The BF1-PC complex possessed higher toxicity towards MCF-7 cells than free BF1, with ІС50 of 9.6 ± 0.8 µМ and 15.8 ± 0.9 µМ, respectively. BF1 and BF1-PC induced an increase in the number of damaged cells of the MDA-MB-231 line with blebbing of plasma membrane, condensed chromatin and/or fragmented nucleus and micronuclei formation. Both BF1 and the BF1-PC complex induced single-strand breaks in DNA and its fragmentation in treated MDA-MB-231 cells. The studied compounds were not bound to plasmid DNA and did not intercalate into DNA molecules.