Chrysomycin A Regulates Proliferation and Apoptosis of Neuroglioma Cells via the Akt/GSK-3β Signaling Pathway In Vivo and In Vitro
Dong-Ni Liu,
Man Liu,
Shan-Shan Zhang,
Yu-Fu Shang,
Wen-Fang Zhang,
Fu-Hang Song,
Hua-Wei Zhang,
Guan-Hua Du,
Yue-Hua Wang
Affiliations
Dong-Ni Liu
Beijing Key Laboratory of Drug Target Identification and New Drug Screening, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China
Man Liu
Beijing Key Laboratory of Drug Target Identification and New Drug Screening, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China
Shan-Shan Zhang
Beijing Key Laboratory of Drug Target Identification and New Drug Screening, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China
Yu-Fu Shang
Beijing Key Laboratory of Drug Target Identification and New Drug Screening, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China
Wen-Fang Zhang
Beijing Key Laboratory of Drug Target Identification and New Drug Screening, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China
Fu-Hang Song
School of Light Industry, Beijing Technology and Business University, Beijing 100048, China
Hua-Wei Zhang
School of Pharmaceutical Sciences, Zhejiang University of Technology, Hangzhou 310014, China
Guan-Hua Du
Beijing Key Laboratory of Drug Target Identification and New Drug Screening, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China
Yue-Hua Wang
Beijing Key Laboratory of Drug Target Identification and New Drug Screening, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China
Glioblastoma (GBM) is a major type of primary brain tumor without ideal prognosis and it is therefore necessary to develop a novel compound possessing therapeutic effects. Chrysomycin A (Chr-A) has been reported to inhibit the proliferation, migration and invasion of U251 and U87-MG cells through the Akt/GSK-3β signaling pathway, but the mechanism of Chr-A against glioblastoma in vivo and whether Chr-A modulates the apoptosis of neuroglioma cells is unclear. The present study aims to elucidate the potential of Chr-A against glioblastoma in vivo and how Chr-A modulates the apoptosis of neuroglioma cells. Briefly, the anti-glioblastoma activity was assessed in human glioma U87 xenografted hairless mice. Chr-A-related targets were identified via RNA-sequencing. Apoptotic ratio and caspase 3/7 activity of U251 and U87-MG cells were assayed via flow cytometry. Apoptosis-related proteins and possible molecular mechanisms were validated via Western blotting. The results showed that Chr-A treatment significantly inhibits glioblastoma progression in xenografted hairless mice, and enrichment analysis suggested that apoptosis, PI3K-Akt and Wnt signaling pathways were involved in the possible mechanisms. Chr-A increased the apoptotic ratio and the activity of caspase 3/7 in U251 and U87-MG cells. Western blotting revealed that Chr-A disturbed the balance between Bax and Bcl-2, activating a caspase cascade reaction and downregulating the expression of p-Akt and p-GSK-3β, suggesting that Chr-A may contribute to glioblastoma regression modulating in the Akt/GSK-3β signaling pathway to promote apoptosis of neuroglioma cells in vivo and in vitro. Therefore, Chr-A may hold therapeutic promise for glioblastoma.
