Potential of Orlistat to induce apoptotic and antiangiogenic effects as well as inhibition of fatty acid synthesis in breast cancer cells.

Autor: Jovankić JV; University of Kragujevac, Faculty of Science, Department of Biology and Ecology, Radoja Domanovića 12, 34000, Kragujevac, Serbia., Nikodijević DD; University of Kragujevac, Faculty of Science, Department of Biology and Ecology, Radoja Domanovića 12, 34000, Kragujevac, Serbia., Milutinović MG; University of Kragujevac, Faculty of Science, Department of Biology and Ecology, Radoja Domanovića 12, 34000, Kragujevac, Serbia. Electronic address: milena.milutinovic@pmf.kg.ac.rs., Nikezić AG; University of Kragujevac, Faculty of Science, Department of Biology and Ecology, Radoja Domanovića 12, 34000, Kragujevac, Serbia., Kojić VV; University of Novi Sad, Faculty of Medicine, Oncology Institute of Vojvodina, Put Dr Goldmana 4, Sremska Kamenica, 21204, Serbia., Cvetković AM; University of Kragujevac, Faculty of Medical Sciences, Department of Surgery, Svetozara Markovića 69, 34000, Kragujevac, Serbia., Cvetković DM; University of Kragujevac, Institute for Information Technologies Kragujevac, Department of Natural Sciences, Jovana Cvijića bb, 34000, Kragujevac, Serbia.
Jazyk: angličtina
Zdroj: European journal of pharmacology [Eur J Pharmacol] 2023 Jan 15; Vol. 939, pp. 175456. Date of Electronic Publication: 2022 Dec 15.
DOI: 10.1016/j.ejphar.2022.175456
Abstrakt: Breast cancer as most often women's cancer is the second cause of mortality worldwide. Research interest increased in testing non-standard drugs to suppress breast cancer progression and become significant supplements in anticancer therapy. The anti-obesity drug Orlistat showed significant ability for modulation of cancer cell metabolism via antiproliferative, proapoptotic, antiangiogenic, antimetastatic, and hypolipidemic effects. The anticancer potential of Orlistat was evaluated by cytotoxicity (MTT assay), type of cell death (AO/EB double staining), determination of redox status parameters (superoxide, hydrogen peroxide, lipid peroxidation, reduced glutathione), and total lipid levels with colorimetric methods, as well on angiogenesis-related (VEGF, MMP-9, CXCR4/CXCL12) and fatty acid synthesis-related (ACLY, ACC, FASN) parameters on gene and protein levels (immunocytochemistry and qPCR). Based on obtained results Orlistat induces significant cytotoxic, proapoptotic, and anti-angiogenic effects in MDA-MB-231, MDA-MB-468 and MCF-7 breast cancer cells, without significant cytotoxic effects on normal MRC-5 cells. It decreased total lipid levels and changed redox status parameters and cancer cell metabolism via suppression of genes and proteins involved and fatty acid synthesis. Based on showed, Orlistat may be an important supplement in antiangiogenic therapy against breast cancer with no side effects on normal cells, making it a good candidate for future clinical trials.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2022 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
Externí odkaz: