Methylxanthines: Potential Therapeutic Agents for Glioblastoma

Pérez-Pérez, Daniel; Reyes-Vidal, Iannel; Chávez-Cortez, Elda Georgina; Sotelo, Julio; Magaña-Maldonado, Roxana

doi:10.3390/ph12030130

Cited by 12 publications

(7 citation statements)

References 96 publications

(82 reference statements)

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“…Surprisingly, no other human studies have been performed, and there are no active clinical trials. A recent review highlights in detail the promising future role for methylxanthines including caffeine in the treatment of glioblastoma [ 98 ].…”

Section: Resultsmentioning

confidence: 99%

Daily Lifestyle Modifications to Improve Quality of Life and Survival in Glioblastoma: A Review

Travers

Litofsky

2021

Brain Sciences

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Survival in glioblastoma remains poor despite advancements in standard-of-care treatment. Some patients wish to take a more active role in their cancer treatment by adopting daily lifestyle changes to improve their quality of life or overall survival. We review the available literature through PubMed and Google Scholar to identify laboratory animal studies, human studies, and ongoing clinical trials. We discuss which health habits patients adopt and which have the most promise in glioblastoma. While results of clinical trials available on these topics are limited, dietary restrictions, exercise, use of supplements and cannabis, and smoking cessation all show some benefit in the comprehensive treatment of glioblastoma. Marital status also has an impact on survival. Further clinical trials combining standard treatments with lifestyle modifications are necessary to quantify their survival advantages.

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Section: Resultsmentioning

confidence: 99%

Daily Lifestyle Modifications to Improve Quality of Life and Survival in Glioblastoma: A Review

Travers

Litofsky

2021

Brain Sciences

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“…Methylxanthines, including theophylline, theobromine and caffeine, have undergone extensive investigation as anti-GBM therapies with mixed results. These findings have been reviewed in greater detail elsewhere [ 69 ]. Briefly, the main mechanism by which these agents act is via phosphodiesterase (PDE) inhibition.…”

Section: Discussionmentioning

confidence: 99%

An Alternative Pipeline for Glioblastoma Therapeutics: A Systematic Review of Drug Repurposing in Glioblastoma

Lyne

Yamini

2021

Cancers

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The treatment of glioblastoma (GBM) remains a significant challenge, with outcome for most patients remaining poor. Although novel therapies have been developed, several obstacles restrict the incentive of drug developers to continue these efforts including the exorbitant cost, high failure rate and relatively small patient population. Repositioning drugs that have well-characterized mechanistic and safety profiles is an attractive alternative for drug development in GBM. In addition, the relative ease with which repurposed agents can be transitioned to the clinic further supports their potential for examination in patients. Here, a systematic analysis of PubMed and ClinicalTrials.gov (August 17, 2020) provides a comprehensive review of primary articles and unpublished trials that use repurposed drugs for the treatment of GBM. The findings demonstrate that numerous drug classes that have a range of initial indications have efficacy against preclinical GBM models and that certain agents have shown significant potential for clinical benefit. With examination in randomized, placebo-controlled trials and the targeting of particular GBM subgroups, it is possible that repurposing can be a cost-effective approach to identify agents for use in multimodal anti-GBM strategies.

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“…The inhibition of glioblastoma cell proliferation has also been achieved by treatment with relatively non-selective PDE inhibitors, such as the methylxanthines theophylline, theobromine, caffeine and IBMX [ 9 , 36 , 37 , 38 , 39 , 40 ]. In general, these compounds decrease glioblastoma cell survival at concentrations above 100 μM, which is similar to the low potency of caffeine and IBMX observed in our experiments (<10% suppression of proliferation at 100 μM).…”

Section: Discussionmentioning

confidence: 99%

Suppression of Proliferation of Human Glioblastoma Cells by Combined Phosphodiesterase and Multidrug Resistance-Associated Protein 1 Inhibition

Kopanitsa¹,

Kopanitsa

Safitri

et al. 2021

IJMS

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The paucity of currently available therapies for glioblastoma multiforme requires novel approaches to the treatment of this brain tumour. Disrupting cyclic nucleotide-signalling through phosphodiesterase (PDE) inhibition may be a promising way of suppressing glioblastoma growth. Here, we examined the effects of 28 PDE inhibitors, covering all the major PDE classes, on the proliferation of the human U87MG, A172 and T98G glioblastoma cells. The PDE10A inhibitors PF-2545920, PQ10 and papaverine, the PDE3/4 inhibitor trequinsin and the putative PDE5 inhibitor MY-5445 potently decreased glioblastoma cell proliferation. The synergistic suppression of glioblastoma cell proliferation was achieved by combining PF-2545920 and MY-5445. Furthermore, a co-incubation with drugs that block the activity of the multidrug resistance-associated protein 1 (MRP1) augmented these effects. In particular, a combination comprising the MRP1 inhibitor reversan, PF-2545920 and MY-5445, all at low micromolar concentrations, afforded nearly complete inhibition of glioblastoma cell growth. Thus, the potent suppression of glioblastoma cell viability may be achieved by combining MRP1 inhibitors with PDE inhibitors at a lower toxicity than that of the standard chemotherapeutic agents, thereby providing a new combination therapy for this challenging malignancy.

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Methylxanthines: Potential Therapeutic Agents for Glioblastoma

Cited by 12 publications

References 96 publications

Daily Lifestyle Modifications to Improve Quality of Life and Survival in Glioblastoma: A Review

Daily Lifestyle Modifications to Improve Quality of Life and Survival in Glioblastoma: A Review

An Alternative Pipeline for Glioblastoma Therapeutics: A Systematic Review of Drug Repurposing in Glioblastoma

Suppression of Proliferation of Human Glioblastoma Cells by Combined Phosphodiesterase and Multidrug Resistance-Associated Protein 1 Inhibition

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