NRF2 modulation in colorectal cancer chemoprevention: integrating traditional medicine with translational strategies against oxidative stress, inflammation, and cancer stem cells.
A Raviteja, Verma Pinki
Abstract
Colorectal cancer (CRC) is an important and significant reason for cancer-related morbidity and mortality globally. Treatment remains challenging due to recurrence, metastasis, and chemoresistance. Evidence shows that oxidative stress, ongoing inflammation, and cancer stem cells (CSCs) play essential functions in CRC development and progression. Nrf2 is a master regulator of cellular redox balance through the Keap1-Nrf2-is signalling pathway. Normal activation of Nrf2 protects colonic cells from oxidative DNA harm and inflammation during initial carcinogenesis. However, sustained Nrf2 activation in tumours encourages chemoresistance, metabolic reprogramming, and CSC upkeep, showing a dual role. Traditional medicine and dietary phytochemicals (curcumin, sulforaphane, resveratrol, EGCG, berberine) can modulate Nrf2 while interacting with NF-κB, Wnt/β-catenin, and Notch pathways. This review synthesises mechanistic and translational evidence on Nrf2 modulation in CRC chemoprevention, stressing conventional medicine-derived agents in modern approaches. It moreover highlights difficulties, limitations, and future viewpoints for precision chemoprevention and personalised interventions.
Key Findings
- Nrf2 plays a dual role in colorectal cancer, protecting normal cells from oxidative damage and inflammation but promoting chemoresistance and cancer stem cell maintenance when persistently activated in tumors.
- Traditional medicine and dietary phytochemicals such as curcumin, sulforaphane, resveratrol, EGCG, and berberine can modulate Nrf2 activity and interact with key signaling pathways including NF-κB, Wnt/β-catenin, and Notch.
- Integrating traditional medicine-derived agents with translational strategies offers a promising approach for precision chemoprevention and personalized interventions in colorectal cancer.
Clinical Significance
Modulating Nrf2 through traditional medicine-derived compounds may provide effective chemopreventive strategies against colorectal cancer by targeting oxidative stress, inflammation, and cancer stem cells, potentially improving patient outcomes and overcoming chemoresistance.
Citation
A Raviteja, Verma Pinki. NRF2 modulation in colorectal cancer chemoprevention: integrating traditional medicine with translational strategies against oxidative stress, inflammation, and cancer stem cells. Naunyn-Schmiedeberg's archives of pharmacology. 2026-Oct-24.