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

Abstract

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.

• Authors: Peng Lv, Weiyao Wang, Zhiyou Cao, Donghai Zhao, Guifang Zhao, Dailin Li, Ling Qi, Junjie Xu
• Journal: Journal of cellular biochemistry (J Cell Biochem) Vol. 120 Issue 1 Pg. 321-331 (01 2019) ISSN: 1097-4644 [Electronic] United States
• PMID: 30171713 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2018 Wiley Periodicals, Inc.

Chemical References

• Butadienes
• CREB1 protein, human
• Cyclic AMP Response Element-Binding Protein
• Nitriles
• Plant Extracts
• U 0126
• Colforsin
• Cyclic AMP
• Mitogen-Activated Protein Kinases
• 1-Methyl-3-isobutylxanthine

Topics

• 1-Methyl-3-isobutylxanthine (pharmacology)
• Apoptosis (drug effects, genetics)
• Brain Neoplasms (metabolism, pathology)
• Butadienes (pharmacology)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Colforsin (pharmacology)
• Cyclic AMP (metabolism)
• Cyclic AMP Response Element-Binding Protein (metabolism)
• Glioma (metabolism, pathology)
• Humans
• Mitogen-Activated Protein Kinases (metabolism)
• Neoplastic Stem Cells (metabolism)
• Nitriles (pharmacology)
• Plant Extracts (pharmacology)
• Plant Roots (chemistry)
• Plectranthus (chemistry)
• Signal Transduction (drug effects)