Thioredoxin-dependent system. Application of inhibitors

Area of Science:

• Biochemistry
• Molecular Biology
• Oncology

Background:

• The thioredoxin (Trx) system is vital for cellular redox homeostasis.
• It regulates protein expression via transcription factor NF-κB and apoptosis regulating kinase (ASK-1).
• The Trx system's dual role in promoting tumor angiogenesis/growth and neoplastic cell apoptosis necessitates targeted inhibition.

Purpose of the Study:

• To identify and investigate compounds that inhibit the thioredoxin system.
• To explore therapeutic strategies targeting Trx and Trx reductase (TrxR) for cancer modulation.

Main Methods:

• Review of existing literature on Trx/TrxR inhibitors.
• Analysis of naturally occurring polyphenolic compounds.
• Examination of synthetic inhibitors including imidazole derivatives, metal complexes, and ebselen.

Main Results:

• Naturally occurring polyphenols inactivate the thioredoxin system.
• Various synthetic compounds demonstrate inhibitory effects on Trx and TrxR.
• Specific inhibitors include imidazole derivatives (Trx) and transition metal complexes, Michael acceptors, nitrosourea, and ebselen (TrxR).

Conclusions:

• Inhibiting the thioredoxin system is a promising strategy for cancer therapy.
• Diverse classes of compounds, both natural and synthetic, show potential as Trx/TrxR inhibitors.
• Ongoing research focuses on discovering novel, selective inhibitors to modulate neoplastic processes.