Kalın, Şeyda Nur; Altay, Ahmet; Budak, Harun

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 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.

Kalındemirtaş, Ferdane Danışman; Kaya, Büşra; Sert, Esra; Şahin, Onur; Kuruca, Serap Erdem; Ülküseven, Bahri

In order to examine the anticancer potential of oxovanadium(IV) complexes with thiosemicarbazone, two new complexes were prepared starting from 2-thenoyltrifluoroacetone-S-methylthiosemicarbazone. The complexes with tetradentate thiosemicarbazone ligand were characterized by elemental analysis, IR, ESI MS, and single-crystal X-ray diffraction analysis. Cytotoxicity on breast cancer cells, MDA-MB-231 and MCF-7, was determined by MTT assay. Cisplatin was positive control and the results were compared with those of the normal cells, HUVEC and 3T3. The complexes exhibited greater activity on cancer cells than cisplatin, but they were cytotoxic at several times higher concentrations in the healthy cells. In our study, the presence of thiophene and fluoro groups in the oxovanadium(IV) complexes with thiosemicarbazone increased greatly the cytotoxic activity of the complexes on breast cancer cells. Moreover, the complexes induced apoptosis-mediated cell death and also reduced the expression of MDR-1 or P-glycoprotein and ABCG2. As a result, the findings indicated that the complexes have selective cytotoxicity on breast cancer cells and can overcome multidrug resistance. These properties of the complexes make it possible to be a potential anticancer drug candidate for breast cancer treatment.