ArticleOncotarget2016
Genistein mediates the selective radiosensitizing effect in NSCLC A549 cells via inhibiting methylation of the keap1 gene promoter region.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers, 1 of them a synthesis that pooled it.
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Who cites it
36 citing papers in PubMed, 1 synthesis or guideline pooled it, 70 citations in OpenAlex.
- Pooled it
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- Advancing cancer radiotherapy: Harnessing radiosensitizers and nanotechnology for enhanced tumor control.International journal of pharmaceutics: X · 2025Review
- Decoding the NRF2-NOTCH Crosstalk in Lung Cancer-An Update.Antioxidants (Basel, Switzerland) · 2025Review
- Enhancement of radiation effects by Plantago major in MCF-7 human breast cancer: an animal study.Discover oncology · 2025Article
- Cancer chemoprevention: signaling pathways and strategic approaches.Signal transduction and targeted therapy · 2025Review
- Genistein Implications in Radiotherapy: Kill Two Birds with One Stone.Molecules (Basel, Switzerland) · 2025Review
- Role of Radioiodine in Cancer Therapy: A Review of the Design and Challenges in Selecting Radioligands from Natural Sources.Drug design, development and therapy · 2025Review
- Clobetasol propionate, a Nrf-2 inhibitor, sensitizes human lung cancer cells to radiation-induced killing via mitochondrial ROS-dependent ferroptosis.Acta pharmacologica Sinica · 2024Article
- Natural products reverse cancer multidrug resistance.Frontiers in pharmacology · 2024Review
- mActa biochimica et biophysica Sinica · 2023Review
- Natural Radiosensitizers in Radiotherapy: Cancer Treatment by Combining Ionizing Radiation with Resveratrol.International journal of molecular sciences · 2022Review
- Dietary Phytochemicals Targeting Nrf2 to Enhance the Radiosensitivity of Cancer.Oxidative medicine and cellular longevity · 2022Review
- Potential Role of Natural Products to Combat Radiotherapy and Their Future Perspectives.Molecules (Basel, Switzerland) · 2021Review
- Flavonoids as an effective sensitizer for anti-cancer therapy: insights into multi-faceted mechanisms and applicability towards individualized patient profiles.The EPMA journal · 2021Review
- The Hallmarks of Flavonoids in Cancer.Molecules (Basel, Switzerland) · 2021Review
- Genistein: An Integrative Overview of Its Mode of Action, Pharmacological Properties, and Health Benefits.Oxidative medicine and cellular longevity · 2021Review
- Radiation Resistance: A Matter of Transcription Factors.Frontiers in oncology · 2021Review
- Epigenetic Scanning ofAntioxidants (Basel, Switzerland) · 2020Article
- Mitochondrial DNA and Neurodegeneration: Any Role for Dietary Antioxidants?Antioxidants (Basel, Switzerland) · 2020Review
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Non-small cell lung cancer (NSCLC) cells often possess a hypermethylated Keap1 promoter, which decreases Keap1 mRNA and protein expression levels, thus impairing the Nrf2-Keap1 pathway and thereby leading to chemo- or radio-resistance. In this study, we showed that genistein selectively exhibited a radiosensitizing effect on NSCLC A549 cells but not on normal lung fibroblast MRC-5 cells. Genistein caused oxidative stress in A549 cells rather than MRC-5 cells, as determined by the oxidation of the ROS-sensitive probe DCFH-DA and oxidative damage marked by MDA, PCO or 8-OHdG content. In A549 instead of MRC-5 cells, genistein reduced the level of methylation in the Keap1 promoter region, leading to an increased mRNA expression, thus effectively inhibited the transcription of Nrf2 to the nucleus, which suppressed the Nrf2-dependent antioxidant and resulted in the upregulation of ROS. Importantly, when combined with radiation, genistein further increased the ROS levels in A549 cells whereas decreasing the radiation-induced oxidative stress in MRC-5 cells, possibly via increasing the expression levels of Nrf2, GSH and HO-1. Moreover, radiation combined with genistein significantly increased cell apoptosis in A549 but not MRC-5 cells. Together, the results herein show that the intrinsic difference in the redox status of A549 and MRC-5 cells could be the target for genistein to selectively sensitize A549 cells to radiation, thereby leading to an increase in radiosensitivity for A549 cells.
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Registered trials
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