Diffractaic acid, a novel TrxR1 inhibitor, induces cytotoxicity, apoptosis, and antimigration in human breast cancer cells

Kalin S. N., ALTAY A., BUDAK H.

CHEMICO-BIOLOGICAL INTERACTIONS, cilt.361, 2022 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 361
  • Basım Tarihi: 2022
  • Doi Numarası: 10.1016/j.cbi.2022.109984
  • Dergi Adı: CHEMICO-BIOLOGICAL INTERACTIONS
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, BIOSIS, CAB Abstracts, Chemical Abstracts Core, EMBASE, MEDLINE, Veterinary Science Database
  • Anahtar Kelimeler: Thioredoxin reductase 1, Lichens, Diffractaic acid, Expression, Enzyme activity, Breast cancer, THIOREDOXIN REDUCTASE, OXIDATIVE STRESS, GENE-EXPRESSION, SYSTEM, METASTASIS, ACTIVATION, MECHANISMS, INVASION, HEALTH, DEATH
  • Atatürk Üniversitesi Adresli: Evet

Özet

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 IC50 values of 51.32 mu g/ml and 87.03 mu g/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.