Bardoxolone Methyl: A Comprehensive Review of Its Role as a Nrf2 Activator in Anticancer Therapeutic Applications
Bardoxolone methyl, also known as CDDO-Me or RTA 402, is a synthetic oleanane triterpenoid that has garnered significant attention as a potent pharmacological activator of the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway. Nrf2 is a master regulator of cellular redox homeostasis, contro...
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MDPI AG
2025-06-01
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| author | Valentina Schiavoni Tiziana Di Crescenzo Valentina Membrino Sonila Alia Sonia Fantone Eleonora Salvolini Arianna Vignini |
| author_facet | Valentina Schiavoni Tiziana Di Crescenzo Valentina Membrino Sonila Alia Sonia Fantone Eleonora Salvolini Arianna Vignini |
| author_sort | Valentina Schiavoni |
| collection | DOAJ |
| description | Bardoxolone methyl, also known as CDDO-Me or RTA 402, is a synthetic oleanane triterpenoid that has garnered significant attention as a potent pharmacological activator of the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway. Nrf2 is a master regulator of cellular redox homeostasis, controlling the expression of genes involved in antioxidant defense, detoxification, and mitochondrial function. By inducing Nrf2 and promoting the transcription of downstream antioxidant response element (ARE)-driven genes, bardoxolone methyl enhances cellular resilience to oxidative stress and inflammation. This mechanism is central not only to its cytoprotective effects but also to its emerging role in oncology. A number of studies investigated the effects of bardoxolone methyl in several malignancies including breast cancer, lung cancer, pancreatic ductal adenocarcinoma, prostate cancer, colorectal cancer, oral and esophageal squamous cell carcinoma, ovarian cancer and glioblastoma. Studies in the literature indicate that bardoxolone methyl exhibits anticancer activity through several mechanisms, including the suppression of cell proliferation, induction of cell cycle arrest and apoptosis, inhibition of epithelial–mesenchymal transition (EMT), and impairment of cancer cell stemness. Additionally, bardoxolone methyl modulates mitochondrial function, reduces glycolytic and oxidative phosphorylation capacities, and induces reactive oxygen species (ROS)-mediated stress responses. In this review, we summarize the available literature regarding the studies which investigated the effects of bardoxolone methyl as anticancer agent. |
| format | Article |
| id | doaj-art-1d93d93aa9164bd3aba7ff30922845a2 |
| institution | Kabale University |
| issn | 1424-8247 |
| language | English |
| publishDate | 2025-06-01 |
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| spelling | doaj-art-1d93d93aa9164bd3aba7ff30922845a22025-08-20T03:56:47ZengMDPI AGPharmaceuticals1424-82472025-06-0118796610.3390/ph18070966Bardoxolone Methyl: A Comprehensive Review of Its Role as a Nrf2 Activator in Anticancer Therapeutic ApplicationsValentina Schiavoni0Tiziana Di Crescenzo1Valentina Membrino2Sonila Alia3Sonia Fantone4Eleonora Salvolini5Arianna Vignini6Department of Clinical Sciences, Polytechnic University of Marche, 60100 Ancona, ItalyDepartment of Clinical Sciences, Polytechnic University of Marche, 60100 Ancona, ItalyDepartment of Clinical Sciences, Polytechnic University of Marche, 60100 Ancona, ItalyDepartment of Clinical Sciences, Polytechnic University of Marche, 60100 Ancona, ItalyScientific Direction, IRCCS INRCA, 60124 Ancona, ItalyDepartment of Clinical Sciences, Polytechnic University of Marche, 60100 Ancona, ItalyDepartment of Clinical Sciences, Polytechnic University of Marche, 60100 Ancona, ItalyBardoxolone methyl, also known as CDDO-Me or RTA 402, is a synthetic oleanane triterpenoid that has garnered significant attention as a potent pharmacological activator of the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway. Nrf2 is a master regulator of cellular redox homeostasis, controlling the expression of genes involved in antioxidant defense, detoxification, and mitochondrial function. By inducing Nrf2 and promoting the transcription of downstream antioxidant response element (ARE)-driven genes, bardoxolone methyl enhances cellular resilience to oxidative stress and inflammation. This mechanism is central not only to its cytoprotective effects but also to its emerging role in oncology. A number of studies investigated the effects of bardoxolone methyl in several malignancies including breast cancer, lung cancer, pancreatic ductal adenocarcinoma, prostate cancer, colorectal cancer, oral and esophageal squamous cell carcinoma, ovarian cancer and glioblastoma. Studies in the literature indicate that bardoxolone methyl exhibits anticancer activity through several mechanisms, including the suppression of cell proliferation, induction of cell cycle arrest and apoptosis, inhibition of epithelial–mesenchymal transition (EMT), and impairment of cancer cell stemness. Additionally, bardoxolone methyl modulates mitochondrial function, reduces glycolytic and oxidative phosphorylation capacities, and induces reactive oxygen species (ROS)-mediated stress responses. In this review, we summarize the available literature regarding the studies which investigated the effects of bardoxolone methyl as anticancer agent.https://www.mdpi.com/1424-8247/18/7/966bardoxolone methylCDDO-MeRTA 402triterpenoid |
| spellingShingle | Valentina Schiavoni Tiziana Di Crescenzo Valentina Membrino Sonila Alia Sonia Fantone Eleonora Salvolini Arianna Vignini Bardoxolone Methyl: A Comprehensive Review of Its Role as a Nrf2 Activator in Anticancer Therapeutic Applications Pharmaceuticals bardoxolone methyl CDDO-Me RTA 402 triterpenoid |
| title | Bardoxolone Methyl: A Comprehensive Review of Its Role as a Nrf2 Activator in Anticancer Therapeutic Applications |
| title_full | Bardoxolone Methyl: A Comprehensive Review of Its Role as a Nrf2 Activator in Anticancer Therapeutic Applications |
| title_fullStr | Bardoxolone Methyl: A Comprehensive Review of Its Role as a Nrf2 Activator in Anticancer Therapeutic Applications |
| title_full_unstemmed | Bardoxolone Methyl: A Comprehensive Review of Its Role as a Nrf2 Activator in Anticancer Therapeutic Applications |
| title_short | Bardoxolone Methyl: A Comprehensive Review of Its Role as a Nrf2 Activator in Anticancer Therapeutic Applications |
| title_sort | bardoxolone methyl a comprehensive review of its role as a nrf2 activator in anticancer therapeutic applications |
| topic | bardoxolone methyl CDDO-Me RTA 402 triterpenoid |
| url | https://www.mdpi.com/1424-8247/18/7/966 |
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