Natural Nrf2 activators modulate antioxidant gene expression and apoptosis in leukemic K-562 cells

Area of Science:

• Pharmacology
• Natural Products Research
• Cancer Biology

Background:

• Natural products (NPs) are vital in traditional medicine and cancer research.
• Their therapeutic effects often involve redox-sensitive pathways, notably the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway.
• Nrf2 regulates antioxidant responses and cellular defense mechanisms crucial for cancer chemoprevention.

Purpose of the Study:

• To evaluate the antioxidant capacity, cytotoxicity, and pro-apoptotic activity of 22 ethnomedicinal natural product extracts.
• To assess the Nrf2-modulating effects of these extracts in a human leukemic K-562 cell model.
• To identify specific natural products with significant chemopreventive potential.

Main Methods:

• Quantification of total phenolic content (TPC) and radical scavenging activity (DPPH, ABTS assays).
• Assessment of cytotoxic effects using the AlamarBlue assay and apoptosis induction via caspase-3 activity.
• Analysis of Nrf2 target gene expression (HO-1, NQO1, GCLC) using RT-qPCR.

Main Results:

• Extracts showed varied antioxidant and cytotoxic activities; Punica granatum, Rhodiola rosea, and Thymus vulgaris exhibited high TPC and antioxidant potential.
• Rhodiola rosea demonstrated the strongest cytotoxic effect, while Hypericum perforatum induced the highest caspase-3 activity.
• Thymus vulgaris, Rhodiola rosea, and others significantly upregulated Nrf2 target genes, with T. vulgaris showing the greatest induction.

Conclusions:

• Traditionally used natural products possess significant pharmacological potential as modulators of redox signaling and inducers of apoptosis in leukemia cells.
• The identified extracts, particularly those activating the Nrf2 pathway, warrant further investigation for cancer chemoprevention and therapy.
• This study validates the ethnomedicinal use of selected NPs and provides a scientific basis for their development.