Methylxanthines: Potential Therapeutic Agents for Glioblastoma
Abstract
1. Introduction
2. Phosphodiesterases in Glioblastoma (GBM)
3. Methylxanthines
3.1. Caffeine
3.2. Theophylline
3.3. Theobromine
4. Methylxanthines and Cellular Differentiation
5. Conclusions
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Main Author (Reference) | Methylxanthine | Type of Study | Relevant Methodology | Relevant Results |
---|---|---|---|---|
Moon et al., 2012 [14] | Theophylline | In vitro | A-172 and U87MG cell lines | Reduces the survival and proliferation |
Nagai et al., 1971 [15] | Theophylline | In vitro | Human glioblastoma cells and glioma cells induced by MC in C57 black mouse | Induces morphological changes |
Sato et al., 1975 [16] | Theophylline | In vitro | Mouse glioma cell line | Induces glial-like morphological changes and expression of S-100 protein. |
Takanaga et al., 2004 [17] | Theophylline | In vitro | C6 cell line | N6,2′-O-dibutyryl cAMP (Bt2AMP) and theophylline caused delayed phosphorylation of STAT3 and expression of GFAP. |
Sugimoto et al., 2014 [18] | Theobromine | In vitro | U87MG cell line | Anti-tumoral and anti-inflammatory effects. Inhibits proliferation and induces apoptosis. |
Stewart et al., 1987 [19] | Caffeine | Clinical | 25 patients with gliomas Caffeine added to cytosine arabinoside plus cisplatin | Presence of caffeine-induced seizures 48% of the patients responded. |
Janss et al., 1998 [20] | Caffeine | In vitro | U251 glioma cells | Caffeine reduced the ID50 and ID90 of cisplatin promoting apoptosis. |
Chen et al., 2014 [21] | Caffeine | In vitro | C6 and U87MG cell lines | Caffeine decreases migration by inhibition of ROCK-focal adhesion complex pathway. |
Sinn et al., 2010 [22] | Caffeine | In vitro | U87MG, T98G and U373MG cells lines | Inhibits PI3K, downregulating the PI3K/Akt pathway and induces apoptosis. |
Ku et al., 2011 [23] | Caffeine | In vivo | Mouse xenograft model of GBM | Inhibits of the IP3R3. |
Phosphodiesterase | Gene Chromosome | Substrate | Main Function | Participation in GBM | Ref. |
---|---|---|---|---|---|
PDE1 | PDE1A, B, C 2q32.1, 12q13.2, 7q14.3 | cAMP and cGMP | Promotes cell proliferation and migration | PDE1C is overexpressed on GBM | [29,30,31,32] |
PDE2 | PDE2A 11q13.4 | cAMP and cGMP | Regulates endothelial permeability and proliferation and nNOS expression. | PDE2A is overexpressed in low grade glioma | [33,34] |
PDE3 | PDE3A, B 12q12.2, 11p15.2 | cAMP and cGMP | Smooth muscle contraction, insulin signaling, blood vessel formation, and antiapoptotic and anti-inflammatory pathways | N. D. | [35,36,37] |
PDE4 | PDE4A, B, C, D 19p13.2, 1p31.3, 19p13.11, 5p11.2-q12.1 | cAMP | Promotes blood vessel formation, monocyte and macrophage activation, and antiapoptotic and anti-inflammatory pathways | PDE4 promotes the tumor growth Hypermethylation of the PDE4C promoter is associated with high malignant grade and reduced overall survival | [36,38,39,40,41] |
PDE5 | PDE5A 4q26 | cGMP | Regulates cell signaling | PDE5 is overexpression correlates with longer overall survival, and its inhibition induces an invasive phenotype of GBM | [7,42] |
PDE6 | PDE6A, B, C 5q32, 4p16.3, 10q24 | cGMP | Participates in rod and cone photoreceptor function | N. D. | [43,44,45] |
PDE7 | PDE7A, B 8q13, 6q23-24 | cAMP | Modulation of T-cell proliferation | PDE7B overexpression induces tumor growth | [46,47,48,49] |
PDE8 | PDE8A, B 15q25.3, 15q13.3 | cAMP | Controls T cells and breast cancer cells motility | PDE8A expression correlates with an increased overall survival | [50,51,52,53] |
PDE9 | PDE9A 21q22.3 | cGMP | Participates in synaptic plasticity and cognitive function | N. D. | [54,55] |
PDE10 | PDE10A 6q26 | cAMP and cGMP | Regulates intracellular signaling and controls striatal gene expression | PDE10A is deleted on GBM tissue | [56,57,58] |
PDE11 | PDE11A 2q31.2 | cAMP and cGMP | Contributes to sperm development | N. D. | [59] |
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Pérez-Pérez, D.; Reyes-Vidal, I.; Chávez-Cortez, E.G.; Sotelo, J.; Magaña-Maldonado, R. Methylxanthines: Potential Therapeutic Agents for Glioblastoma. Pharmaceuticals 2019, 12, 130. https://doi.org/10.3390/ph12030130
Pérez-Pérez D, Reyes-Vidal I, Chávez-Cortez EG, Sotelo J, Magaña-Maldonado R. Methylxanthines: Potential Therapeutic Agents for Glioblastoma. Pharmaceuticals. 2019; 12(3):130. https://doi.org/10.3390/ph12030130
Chicago/Turabian StylePérez-Pérez, Daniel, Iannel Reyes-Vidal, Elda Georgina Chávez-Cortez, Julio Sotelo, and Roxana Magaña-Maldonado. 2019. "Methylxanthines: Potential Therapeutic Agents for Glioblastoma" Pharmaceuticals 12, no. 3: 130. https://doi.org/10.3390/ph12030130
APA StylePérez-Pérez, D., Reyes-Vidal, I., Chávez-Cortez, E. G., Sotelo, J., & Magaña-Maldonado, R. (2019). Methylxanthines: Potential Therapeutic Agents for Glioblastoma. Pharmaceuticals, 12(3), 130. https://doi.org/10.3390/ph12030130