Investigation of Thioredoxin Reductase-Targeted Anticancer Effect of Diffractaic Acid on Human Lung Cancer


Günaydın Ş., Karaca E., Kalın Ş., Altay A., Budak H.

3RD EURASİA BİOCHEMİCAL APPROACHES & TECHNOLOGİES (EBAT), Antalya, Türkiye, 4 - 07 Kasım 2021, ss.85

  • Yayın Türü: Bildiri / Özet Bildiri
  • Basıldığı Şehir: Antalya
  • Basıldığı Ülke: Türkiye
  • Sayfa Sayıları: ss.85
  • Erzincan Binali Yıldırım Üniversitesi Adresli: Evet

Özet

Lung cancer, the leading cause of cancer-related deaths is the most common cancer incidence in both men and women worldwide.1 Thioredoxin reductase (TRXR1), which plays a role in the regulation of intracellular redox balance, is overexpressed in many cancer types including lung cancer. Recently, chemotherapeutic agents targeting the thioredoxin system have been frequently investigated in cancer treatment.2,3 In literature, it has been reported that diffractaic acid, which is the secondary metabolite of lichen, has antioxidant, antitumoral, and anticancer activities. It also inhibits TRXR, purified from rat lung.4,5 However, the TRXR1-targeted anticancer effect of diffractaic acid on human lung cancer (A549) has not been investigated so far. In this study, first of all, the effect of diffractaic acid on viability of A549 cells was investigated by cell proliferation (XTT) assay. It was determined that diffractaic acid had the most cytotoxic effect against A549 cells with an IC50 value of 46.37±1.92 μg/mL at 48 hours. The effect of diffractaic acid on the apoptotic pathway in A549 cells was examined by Real-Time PCR (qPCR), and it was shown that the increase in BAX/BCL2 ratio (p<0.01) and P53 (p<0.0001) gene expressions induced the apoptotic cell death. And then, quantitative protein expression and enzyme activity of TRXR1 were investigated by western blot and DTNB methods, respectively. According to the results, although no significant difference in the quantitative protein expression of TRXR1 was observed, the enzyme activity of TRXR1 was significantly decreased in A549 cells. In conclusion, diffractaic acid showed anticancer activity by targeting TRXR1 in A549 cells and this lichen acid may be evaluated as a potential chemotherapeutic agent. But, it still needs to be investigated in detail with further study.