ReviewPharmaceuticals (Basel, Switzerland)2023
Alkaloids as Natural NRF2 Inhibitors: Chemoprevention and Cytotoxic Action in Cancer.
Review in Pharmaceuticals (Basel, Switzerland), 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 23 citations in OpenAlex.
- Neurons Die Not by One Hit, but by Signaling Convergence.Molecular neurobiology · 2026Review
- Risks, Benefits, and Molecular Targets of Fenugreek Administration in the Treatment of Hepatocellular Carcinoma.Cancers · 2026Review
- Nrf2 Modulation by Natural Compounds in Aging, Neurodegeneration, and Neuropathic Pain.Pharmaceutics · 2026Review
- The addictive and neurotoxicological evaluation ofIBRO neuroscience reports · 2025Article
- Trigonelline activates NRF2 and awakens dormant ovarian follicles to promote pregnancy in aging mice.iScience · 2025Article
- The Role of Phytochemicals in Aging and Aging-Related Diseases.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Oxidative stress in cancer: from tumor and microenvironment remodeling to therapeutic frontiers.Molecular cancer · 2025Review
- Review
- Fenugreek inhibits cathepsin G activity and suppresses the progression of malignant phenotypes in MCF-7 cells.Biochemistry and biophysics reports · 2025Article
- Utilizing Indigenous Flora in East Africa for Breast Cancer Treatment: An Overview.Anti-cancer agents in medicinal chemistry · 2025Review
- The implication of aberrant NRF2 activation in management of female cancers.Frontiers in oncology · 2025Review
- NRF2 Modulators of Plant Origin and Their Ability to Overcome Multidrug Resistance in Cancers.International journal of molecular sciences · 2024Review
- Identification of Penexanthone A as a Novel Chemosensitizer to Induce Ferroptosis by Targeting Nrf2 in Human Colorectal Cancer Cells.Marine drugs · 2024Article
- Crebanine mitigates glucocorticoid-induced osteonecrosis of the femoral head by restoring bone remodelling homeostasis via attenuating oxidative stress.Journal of cellular and molecular medicine · 2024Article
- The role and mechanism of cinnamaldehyde in cancer.Journal of food and drug analysis · 2024Review
- Pharmacological Activities, Therapeutic Effects, and Mechanistic Actions of Trigonelline.International journal of molecular sciences · 2024Review
- Natural products targeting the MAPK-signaling pathway in cancer: overview.Journal of cancer research and clinical oncology · 2024Review
- Ferroptosis in Cancer Therapy: Mechanisms, Small Molecule Inducers, and Novel Approaches.Drug design, development and therapy · 2024Review
- A state-of-the-art review on the NRF2 in Hepatitis virus-associated liver cancer.Cell communication and signaling : CCS · 2023Review
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Being a controller of cytoprotective actions, inflammation, and mitochondrial function through participating in the regulation of multiple genes in response to stress-inducing endogenous or exogenous stressors, the transcription factor Nuclear Factor Erythroid 2-Related Factor 2 (NRF2) is considered the main cellular defense mechanism to maintain redox balance at cellular and tissue level. While a transient activation of NRF2 protects normal cells under oxidative stress, the hyperactivation of NRF2 in cancer cells may help them to survive and to adapt under oxidative stress. This can be detrimental and related to cancer progression and chemotherapy resistance. Therefore, inhibition of NRF2 activity may be an effective approach for sensitizing cancer cells to anticancer therapy. In this review, we examine alkaloids as NRF2 inhibitors from natural origin, their effects on cancer therapy, and/or as sensitizers of cancer cells to anticancer chemotherapeutics, and their potential clinical applications. Alkaloids, as inhibitor of the NRF2/KEAP1 signaling pathway, can have direct (berberine, evodiamine, and diterpenic aconitine types of alkaloids) or indirect (trigonelline) therapeutic/preventive effects. The network linking alkaloid action with oxidative stress and NRF2 modulation may result in an increased NRF2 synthesis, nuclear translocation, as well in a downstream impact on the synthesis of endogenous antioxidants, effects strongly presumed to be the mechanism of action of alkaloids in inducing cancer cell death or promoting sensitivity of cancer cells to chemotherapeutic agents. In this regard, the identification of additional alkaloids targeting the NRF2 pathway is desirable and the information arising from clinical trials will reveal the potential of these compounds as a promising target for anticancer therapy.
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