Fsk and IBMX inhibit proliferation and proapoptotic of glioma stem cells via activation of cAMP signaling pathway

• Published in: Journal of cellular biochemistry 2019-01, Vol.120 (1), p.321-331
• Main Authors: Lv, Peng, Wang, Weiyao, Cao, Zhiyou, Zhao, Donghai, Zhao, Guifang, Li, Dailin, Qi, Ling, Xu, Junjie
• Format: Article
• Language: English
• Subjects: 1-Methyl-3-isobutylxanthine - pharmacology; Apoptosis; Apoptosis - drug effects; Apoptosis - genetics; Brain Neoplasms - metabolism; Brain Neoplasms - pathology; Butadienes - pharmacology; cAMP; Cell Line, Tumor; Cell proliferation; Cell Proliferation - drug effects; Colforsin - pharmacology; Cyclic AMP - metabolism; Cyclic AMP response element-binding protein; Cyclic AMP Response Element-Binding Protein - metabolism; Forskolin; Fsk‐IBMX; Gene expression; Glioma; Glioma - metabolism; Glioma - pathology; Glioma cells; Growth rate; GSCs; Humans; MAP kinase; MAPK; Mitogen-Activated Protein Kinases - metabolism; Neoplastic Stem Cells - metabolism; Nitriles - pharmacology; Plant Extracts - pharmacology; Plant Roots - chemistry; Plectranthus - chemistry; Polymerase chain reaction; proliferation; Proteins; Reverse transcription; Signal transduction; Signal Transduction - drug effects; Signaling; signaling pathway; Stem cells
• ISSN: 0730-2312; 1097-4644
• DOI: 10.1002/jcb.27364

Objective We aimed to find out the underlying mechanism of forskolin (Fsk) and 3‐isobutyl‐1‐methylxanthine (IBMX) on glioma stem cells (GSCs). Methods The expression of cAMP‐related protein CREB and pCREB as well as apoptosis‐related proteins were detected through Western blot analysis. The level of proliferation and growth rate of human GSCs was measured through thiazolyl blue tetrazolium bromide assay and stem cells forming sphere assay. The apoptosis‐related gene expression was measured through reverse transcription‐polymerase chain reaction. Results cAMP signaling pathway was activated in GSCs with Fsk‐IBMX administration. Fsk‐IBMX could inhibit the proliferation as well as invasion and promote the apoptosis of U87 cells. Besides, U0126 could inhibit MAPK signaling pathway to increase the sensitivity of GSCs to cAMP signaling pathway. As a result, Fsk‐IBMX combined with U0126 had more negative effect on GSCs. Conclusions The relationship of cAMP and MAPK signaling pathway in GSCs may provide a potential therapeutic strategy in glioma. The relationship of cAMP and MAPK signaling pathway in GSCs may provide a potential therapeutic strategy in glioma.