Jovankić Jovana V, Nikodijević Danijela D, Milutinović Milena G, Nikezić Aleksandra G, Kojić Vesna V, Cvetković Aleksandar M, Cvetković Danijela M
University of Kragujevac, Faculty of Science, Department of Biology and Ecology, Radoja Domanovića 12, 34000, Kragujevac, Serbia.
University of Kragujevac, Faculty of Science, Department of Biology and Ecology, Radoja Domanovića 12, 34000, Kragujevac, Serbia.
Eur J Pharmacol. 2023 Jan 15;939:175456. doi: 10.1016/j.ejphar.2022.175456. Epub 2022 Dec 15.
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.
乳腺癌作为女性最常见的癌症，是全球第二大致死原因。对测试非标准药物以抑制乳腺癌进展的研究兴趣增加，这些药物成为抗癌治疗中的重要补充。抗肥胖药物奥利司他通过抗增殖、促凋亡、抗血管生成、抗转移和降血脂作用，显示出显著调节癌细胞代谢的能力。通过细胞毒性（MTT 法）、细胞死亡类型（AO/EB 双重染色）、氧化还原状态参数（超氧化物、过氧化氢、脂质过氧化、还原型谷胱甘肽）的测定以及比色法测定总脂质水平，还在基因和蛋白质水平（免疫细胞化学和 qPCR）上检测血管生成相关（VEGF、MMP-9、CXCR4/CXCL12）和脂肪酸合成相关（ACLY、ACC、FASN）参数，评估了奥利司他的抗癌潜力。基于获得的结果，奥利司他在 MDA-MB-231、MDA-MB-468 和 MCF-7 乳腺癌细胞中诱导显著的细胞毒性、促凋亡和抗血管生成作用，而对正常 MRC-5 细胞无显著细胞毒性作用。它降低了总脂质水平，通过抑制相关基因和蛋白质以及脂肪酸合成改变了氧化还原状态参数和癌细胞代谢。基于上述结果，奥利司他可能是抗乳腺癌血管生成治疗中的重要补充药物，对正常细胞无副作用，使其成为未来临床试验的良好候选药物。
