Kalın Şeyda Nur, Altay Ahmet, Budak Harun
Atatürk University, Science Faculty, Department of Molecular Biology and Genetics, 25240, Erzurum, Turkey; Atatürk University, East Anatolia High Technology Application and Research Center (DAYTAM), 25240, Erzurum, Turkey.
Erzincan Binali Yıldırım University, Faculty of Science and Arts, Department of Chemistry, 24002, Erzincan, Turkey.
Chem Biol Interact. 2022 Jul 1;361:109984. doi: 10.1016/j.cbi.2022.109984. Epub 2022 May 13.
Breast cancer represents one of the most frequently encountered cancer types among women worldwide. Thioredoxin reductase 1 (TrxR1) is a therapeutic target for breast cancer therapy due to its overexpression in tumor cells. The current research aims to determine the anticancer effect of diffractaic acid, a lichen acid, in breast cancer, and research whether the anticancer effect of diffractaic acid occurs through TrxR1 targeting. According to the XTT assay results, diffractaic acid induced cytotoxicity in both MCF-7 and MDA-MB-453 cells with IC values of 51.32 μg/ml and 87.03 μg/ml, respectively. Flow cytometry and cell migration analyses revealed the apoptotic, necrotic, and antimigratory effects of diffractaic acid. qPCR analysis indicated the upregulation of the BAX/BCL2 ratio and the P53 gene in MCF-7 cells with only the P53 gene in MDA-MB-453 cells. The gene, protein, and enzyme activity of TrxR1 were suppressed in MCF-7 cells, whereas only enzyme activity was suppressed in MDA-MB-453 cells. These findings illustrate the anticancer effect of diffractaic acid on breast cancer targeting TrxR1. In conclusion, these data reveal that diffractaic acid may be considered an effective therapeutic agent for breast cancer treatment.
乳腺癌是全球女性中最常见的癌症类型之一。硫氧还蛋白还原酶1（TrxR1）因其在肿瘤细胞中的过表达而成为乳腺癌治疗的一个靶点。当前的研究旨在确定地衣酸——地弗酸的抗癌作用，并研究地弗酸的抗癌作用是否通过靶向TrxR1而发生。根据XTT检测结果，地弗酸在MCF-7和MDA-MB-453细胞中均诱导了细胞毒性，IC值分别为51.32μg/ml和87.03μg/ml。流式细胞术和细胞迁移分析揭示了地弗酸的凋亡、坏死和抗迁移作用。qPCR分析表明，MCF-7细胞中BAX/BCL2比值和P53基因上调，而MDA-MB-453细胞中只有P53基因上调。MCF-7细胞中TrxR1的基因、蛋白和酶活性受到抑制，而MDA-MB-453细胞中只有酶活性受到抑制。这些发现说明了地弗酸对靶向TrxR1的乳腺癌具有抗癌作用。总之，这些数据表明地弗酸可被视为一种有效的乳腺癌治疗药物。
