Your browser doesn't support javascript.
loading
CT2-3 induces cell cycle arrest and apoptosis in rheumatoid arthritis fibroblast-like synoviocytes through regulating PI3K/AKT pathway.
Chen, Jian; Lin, Xian; Liu, Kangdi; He, Juan; Li, Xin; Zhang, Chuchu; Deng, Yongxing; Luo, Lianxiang; Tao, Cheng; Wang, Qingwen.
Afiliación
  • Chen J; Department of Rheumatism and Immunology, Peking University Shenzhen Hospital, Shenzhen, 518036, China; Institute of Immunology and Inflammatory Diseases, Shenzhen Peking University-The Hong Kong University of Science and Technology Medical Center, Shenzhen Key Laboratory of Inflammatory and Immunolo
  • Lin X; Department of Rheumatism and Immunology, Peking University Shenzhen Hospital, Shenzhen, 518036, China; Institute of Immunology and Inflammatory Diseases, Shenzhen Peking University-The Hong Kong University of Science and Technology Medical Center, Shenzhen Key Laboratory of Inflammatory and Immunolo
  • Liu K; The First Clinical College, Guangdong Medical University, Zhanjiang, 524023, China.
  • He J; Department of Rheumatism and Immunology, Peking University Shenzhen Hospital, Shenzhen, 518036, China; Institute of Immunology and Inflammatory Diseases, Shenzhen Peking University-The Hong Kong University of Science and Technology Medical Center, Shenzhen Key Laboratory of Inflammatory and Immunolo
  • Li X; Guangdong Provincial Key Laboratory of Research and Development of Natural Drugs, and School of Pharmacy, Guangdong Medical University, Dongguan, 523808, China.
  • Zhang C; Guangdong Provincial Key Laboratory of Research and Development of Natural Drugs, and School of Pharmacy, Guangdong Medical University, Dongguan, 523808, China.
  • Deng Y; Guangdong Provincial Key Laboratory of Research and Development of Natural Drugs, and School of Pharmacy, Guangdong Medical University, Dongguan, 523808, China.
  • Luo L; The Marine Biomedical Research Institute, Guangdong Medical University, Zhanjiang, 524023, China. Electronic address: luolianxiang321@gdmu.edu.cn.
  • Tao C; Guangdong Provincial Key Laboratory of Research and Development of Natural Drugs, and School of Pharmacy, Guangdong Medical University, Dongguan, 523808, China. Electronic address: taocheng@gdmu.edu.cn.
  • Wang Q; Department of Rheumatism and Immunology, Peking University Shenzhen Hospital, Shenzhen, 518036, China; Institute of Immunology and Inflammatory Diseases, Shenzhen Peking University-The Hong Kong University of Science and Technology Medical Center, Shenzhen Key Laboratory of Inflammatory and Immunolo
Eur J Pharmacol ; 956: 175871, 2023 Oct 05.
Article en En | MEDLINE | ID: mdl-37406849
Rheumatoid arthritis (RA) is a kind of chronic autoimmune disease. The existing therapies encountered several challenges. Therefore, continued novel anti-RA drug discovery remains necessary for RA therapy. Recently, our group reported a novel compound named CT2-3, which could be realized as a hybrid of the natural product magnolol and phthalimide and exhibited anti-lung cancer activity. However, the effect of CT2-3 on RA is unclear. Here, we aim to explore the effect and potential mechanism of CT2-3 on the abnormal functions of RA-fibroblast-like synoviocytes (RA-FLSs). In this study, we identified the important role of the dysregulated cell cycle and apoptosis of RA-FLSs in RA progression. Interestingly, we found that CT2-3 inhibited the proliferation and DNA replication of primary RA-FLSs and immortalized RA-FLSs namely MH7A. In addition, CT2-3 downregulated the mRNA and protein expression of cyclin-dependent kinase 2 (CDK2), cyclin A2, and cyclin B1, resulting in cell cycle arrest of primary RA-FLSs and MH7A cells. Also, CT2-3 downregulated the level of B-cell lymphoma-2 (Bcl-2), and increased the level of Bcl-2 associated X (Bax), contributing to apoptosis of primary RA-FLSs and MH7A cells. Furthermore, differential analyses of RNA-sequencing, Western blot, and network pharmacological analysis confirmed that CT2-3 inhibited phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) pathway of primary RA-FLSs and MH7A cells. In conclusion, CT2-3 induces cell cycle arrest and apoptosis in RA-FLSs through modulating PI3K/AKT pathway, which may serve as a potential lead compound for further novel small molecule anti-RA drug development.
Asunto(s)
Palabras clave
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Artritis Reumatoide / Sinoviocitos Límite: Humans Idioma: En Revista: Eur J Pharmacol Año: 2023 Tipo del documento: Article Pais de publicación: Países Bajos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Artritis Reumatoide / Sinoviocitos Límite: Humans Idioma: En Revista: Eur J Pharmacol Año: 2023 Tipo del documento: Article Pais de publicación: Países Bajos