Mei Luo,Yuelian Wang,Xiaodong Liu,Lin Liu,Li Zhu,Guo Chen,Qing Ye,Chengshi He,Xujue Xiao,Jike Li
Among the spectrum of digestive system cancers, hepatocellular carcinoma (HCC) poses a particularly formidable challenge due to its poor prognosis. Geniposide, an iridoid glucoside extracted from the fruit of Gardenia jasminoides Ellis, exhibits a diverse array of biological activities. The goal of this study is to delineate the specific roles and underlying mechanisms of geniposide on the progression of HCC. Cell viability, apoptosis and migration of Huh7 and HepG2 cells were, respectively, assessed via CCK-8, flow cytometry and trans-well assays. The level of reactive oxygen species (ROS) was assessed with a dihydroethidium (DHE) probe. The measurement of mitochondrial membrane potential (MMP) was conducted using JC-1 staining. Ferroptosis-related markers were evaluated by Western Blot assay. Transcriptome sequencing was performed in HCC cells both treated and untreated with geniposide. In vivo experiments were applied with the subcutaneous xenograft tumor model. In vitro experiments revealed that geniposide exerted a concentration-dependent suppression on cell viability and migration, concurrently eliciting apoptosis in HCC cells. Ferroptosis was identified as the main form of geniposide-induced cell death in HCC. Geniposide promoted the iron ions levels, ROS accumulation, and the expression of ferroptosis markers, which were partially reversed by the addition of deferoxamine (DFO, ferroptosis inhibitor). Intersection analysis was applied between upregulated genes of HCC cells and ferroptosis-related genes. DUOX1 was proven to be involved in geniposide-mediated roles in HCC. In vivo experiments further clarified the suppressive effects of geniposide on tumors. Geniposide treatment increased intracellular iron ions and induced ferroptosis in HCC. Geniposide attenuated tumor progression and oxidative stress via DUOX1-mediated ferroptosis.
Bangrong Cai,Mengya Liu,Jinxing Li,Dujuan Xu,Jiansheng Li
Chronic obstructive pulmonary disease (COPD) is widely recognized as a global public health problem and the third leading cause of mortality worldwide by 2020. Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is a dual-specificity protein and lipid phosphatase that plays an important role in COPD. However, the redox regulation of PTEN in the development of COPD was poorly studied. Our results showed that cigarette smoke extract (CSE) could oxidize PTEN in a time-dependent manner in BEAS-2B cells, whereas PTEN oxidation exposed to CSE was delayed compared to that of H 2 O 2. Additionally, we found that ROS derived from DUOX1 and 2 of NADPH oxidases were mainly responsible for oxidative inactivation PTEN, also simultaneously led to Trx-1 inactivation by dimerization . Oxidative mechanism of PTEN exposed to CSE was mediated by forming a disulfide bond between Cys 71 and Cys 124 , similar to H 2 O 2 . Inactivation of PTEN resulted in the increased phosphorylation of Akt. In conclusion, CSE exposure could elevate the intracellular ROS mainly from DUOX1 and 2 to oxidize PTEN and Trx-1 resulting in Akt activation, eventually cause the occurrence of COPD, suggesting that PTEN is a potential target for new therapies in COPD.
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