Cyboran-Mikołajczyk Sylwia, Matczak Karolina, Kaźmierczak Teresa, Trochanowska-Pauk Natalia, Walski Tomasz, Bohara Raghvendra, Bukowski Karol, Krawczyk-Łebek Agnieszka, Kostrzewa-Susłow Edyta
Department of Physics and Biophysics, Faculty of Biotechnology and Food Sciences, Wrocław University of Environmental and Life Sciences, Norwida 25 St., 50-375 Wrocław, Poland.
Department of Medical Biophysics, Faculty of Biology and Environmental Protection, University of Lodz, Pomorska 141/143 St., 90-236 Lodz, Poland.
Cells. 2025 Aug 21;14(16):1299. doi: 10.3390/cells14161299.
In the pursuit of novel anticancer therapies, assessing their selectivity and safety profile towards healthy cells is crucial. This study investigated chlorochalcones, derivatives of 2'-hydroxychalcone containing a chlorine atom, for their impact on human breast cancer cells (MCF-7 and MDA-MB-231), healthy blood cells (erythrocytes, peripheral blood mononuclear cells (PBMCs), platelets), and microvascular endothelial cells (HMEC-1). Our findings demonstrated that chlorochalcones did not detrimentally affect erythrocytes, showing no hemolysis or preserving osmotic resistance and transmembrane potential. They also exhibited minimal impact on normal PBMC viability and varying effects on platelet metabolic activity at therapeutic concentrations. Importantly, these derivatives displayed lower toxicity towards HMEC-1 endothelial cells than towards breast cancer cells, indicating a degree of selectivity. Chlorochalcones have high antiproliferative activity against cancer cells, primarily by inducing apoptosis with virtually no significant impact on cell cycle progression. Their mechanism of action involves the modulation of reactive oxygen species (ROS) levels and induction of mitochondrial dysfunction, including membrane depolarization and reduced mitochondrial mass. Biological activity, including toxicity and ROS modulation, is dependent on the position and number of chlorine atoms. In conclusion, this study highlights the ability of chlorochalcones to effectively target malignant cells while sparing normal circulatory and endothelial cells, thus positioning them as a promising class of candidates for further anticancer drug development.
在寻求新型抗癌疗法的过程中，评估它们对健康细胞的选择性和安全性至关重要。本研究调查了含氯原子的2'-羟基查耳酮衍生物氯代查耳酮对人乳腺癌细胞（MCF-7和MDA-MB-231）、健康血细胞（红细胞、外周血单个核细胞（PBMC）、血小板）以及微血管内皮细胞（HMEC-1）的影响。我们的研究结果表明，氯代查耳酮不会对红细胞产生有害影响，未出现溶血现象，或保持了渗透压耐受性和跨膜电位。在治疗浓度下，它们对正常PBMC活力的影响也最小，对血小板代谢活性有不同程度的影响。重要的是，这些衍生物对HMEC-1内皮细胞的毒性低于对乳腺癌细胞的毒性，表明具有一定程度的选择性。氯代查耳酮对癌细胞具有高抗增殖活性，主要通过诱导细胞凋亡，而对细胞周期进程几乎没有显著影响。它们的作用机制涉及调节活性氧（ROS）水平和诱导线粒体功能障碍，包括膜去极化和线粒体质量减少。包括毒性和ROS调节在内的生物学活性取决于氯原子的位置和数量。总之，本研究突出了氯代查耳酮有效靶向恶性细胞同时 sparing正常循环细胞和内皮细胞的能力，因此使其成为进一步抗癌药物开发的一类有前景的候选物。 （注：“sparing”原文可能有误，推测应为“sparing”，意为“使 spared免受损害、使 spared不参与”，这里翻译为“ sparing正常循环细胞和内皮细胞”）
