Inhibition of thioredoxin reductase 1 by vulpinic acid suppresses the proliferation and migration of human breast carcinoma

Kalın Ş. N., Altay A., Budak H.

LIFE SCIENCES, cilt.310, sa.1, ss.1-10, 2022 (SCI-Expanded)

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 310 Sayı: 1
  • Basım Tarihi: 2022
  • Doi Numarası: 10.1016/j.lfs.2022.121093
  • Dergi Adı: LIFE SCIENCES
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, BIOSIS, CAB Abstracts, Chimica, EMBASE, MEDLINE, Veterinary Science Database
  • Sayfa Sayıları: ss.1-10
  • Erzincan Binali Yıldırım Üniversitesi Adresli: Evet

Özet

Aims

It was aimed to investigate the thioredoxin reductase 1 (TrxR1)-targeted anticancer effect of vulpinic (VA) and lecanoric (LA) acids, which are lichen secondary metabolites, on breast cancer MCF-7 and MDA-MB-453 cell lines, and to compare the effectiveness of this potential effect against commercial chemotherapeutic drugs carboplatin and docetaxel.

Main methods

The anticancer effects of both lichen metabolites were evaluated by XTT, flow cytometry analysis, cell scratch, and transwell migration assays. Apoptotic results were also confirmed by qPCR and western blot. Changes in TrxR1 were investigated in gene and protein expressions and enzyme activity levels.

Key findings

VA suppressed the proliferation of MCF-7 and MDA-MB-453 cells in a dose- and time-dependent manner, and the IC50 values were calculated as 22.92 μg/ml and 95.65 μg/ml, respectively. As for LA, it did not have a considerable antiproliferative effect on both cell lines. VA had stronger cytotoxicity than both chemotherapeutic drug in MCF-7 cells and showed antiproliferative activity closer to carboplatin in MDA-MB-453 cells. qPCR, western blot, and flow cytometry analysis results revealed that VA did not induce apoptosis in both cell lines. In contrast, VA caused cell cycle arrest, significantly. Migration assay results showed that VA suppressed migration in both cells. VA induced the gene expression of TrxR1 while inhibiting its protein expression and enzymatic activity in both cell lines.

Significance

The findings reveal that vulpinic acid may be a novel inhibitor candidate on TrxR1 and could be considered a potential chemotherapeutic agent for breast cancer treatment, especially in MCF-7 cells.