Schiavoni Valentina, Di Crescenzo Tiziana, Membrino Valentina, Alia Sonila, Fantone Sonia, Salvolini Eleonora, Vignini Arianna
Department of Clinical Sciences, Polytechnic University of Marche, 60100 Ancona, Italy.
Scientific Direction, IRCCS INRCA, 60124 Ancona, Italy.
Pharmaceuticals (Basel). 2025 Jun 27;18(7):966. doi: 10.3390/ph18070966.
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.
巴多昔芬甲基，也称为CDDO-Me或RTA 402，是一种合成的齐墩果烷三萜类化合物，作为核因子红细胞2相关因子2（Nrf2）途径的有效药理激活剂而备受关注。Nrf2是细胞氧化还原稳态的主要调节因子，控制参与抗氧化防御、解毒和线粒体功能的基因表达。通过诱导Nrf2并促进下游抗氧化反应元件（ARE）驱动基因的转录，巴多昔芬甲基增强细胞对氧化应激和炎症的抵抗力。这一机制不仅是其细胞保护作用的核心，也是其在肿瘤学中新兴作用的核心。多项研究调查了巴多昔芬甲基在包括乳腺癌、肺癌、胰腺导管腺癌、前列腺癌、结直肠癌、口腔和食管鳞状细胞癌、卵巢癌和胶质母细胞瘤在内的多种恶性肿瘤中的作用。文献研究表明，巴多昔芬甲基通过多种机制发挥抗癌活性，包括抑制细胞增殖、诱导细胞周期停滞和凋亡、抑制上皮-间质转化（EMT）以及损害癌细胞干性。此外，巴多昔芬甲基调节线粒体功能，降低糖酵解和氧化磷酸化能力，并诱导活性氧（ROS）介导的应激反应。在本综述中，我们总结了有关研究巴多昔芬甲基作为抗癌药物作用的现有文献。
