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

Abstract

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.

• Authors: Şeyda Nur Kalın, Ahmet Altay, Harun Budak
• Journal: Life sciences (Life Sci) Vol. 310 Pg. 121093 (Dec 01 2022) ISSN: 1879-0631 [Electronic] Netherlands
• PMID: 36270425 (Publication Type: Journal Article)
• Copyright: Copyright © 2022 Elsevier Inc. All rights reserved.

Chemical References

• vulpinic acid
• Thioredoxin Reductase 1
• Carboplatin

Topics

• Humans
• Female
• Thioredoxin Reductase 1
• Carboplatin (pharmacology, therapeutic use)
• Breast Neoplasms (pathology)
• MCF-7 Cells
• Apoptosis
• Cell Proliferation
• Cell Line, Tumor