Chlorogenic acid (CGA) has demonstrated anti-tumor effects across various cancers, but its role in cholangiocarcinoma (CCA) remains unclear. Our study revealed CGA’s potent anti-tumor effects on CCA, significantly suppressing cell proliferation, migration, colony formation, and invasion while inhibiting the epithelial–mesenchymal transition. CGA induced apoptosis, modulated cell cycle progression, and exhibited a stable binding affinity to AKR1B10 in CCA. AKR1B10 was highly expressed in RBE cells, and CGA treatment reduced AKR1B10 expression. Knocking out AKR1B10 inhibited the proliferation of RBE cells, whereas the overexpression of AKR1B10 promoted their proliferation. Additionally, CGA suppressed the proliferation of RBE cells with AKR1B10 overexpression. Mechanistically, AKR1B10 activated AKT, and CGA exerted its inhibitory effect by reducing AKR1B10 levels, thereby suppressing AKT activation. Furthermore, CGA facilitated the polarization of tumor-associated macrophages towards an anti-tumor phenotype and enhanced T-cell cytotoxicity. These findings underscore CGA’s potential as a promising therapeutic agent for CCA treatment.
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.
危险品化学品经营许可证（带存储）