Abstract
Glioblastoma (GBM) is the most common and aggressive primary brain tumor. Currently, treatment is ineffective and the median overall survival is 20.9 months. The poor prognosis of GBM is a consequence of several altered signaling pathways that favor the proliferation and survival of neoplastic cells. One of these pathways is the deregulation of phosphodiesterases (PDEs). These enzymes participate in the development of GBM and may have value as therapeutic targets to treat GBM. Methylxanthines (MXTs) such as caffeine, theophylline, and theobromine are PDE inhibitors and constitute a promising therapeutic anti-cancer agent against GBM. MTXs also regulate various cell processes such as proliferation, migration, cell death, and differentiation; these processes are related to cancer progression, making MXTs potential therapeutic agents in GBM.
Highlights
Glioblastoma (GBM) is the most aggressive and most frequent primary malignant tumor of the central nervous system (CNS) [1]
Due to the ineffectiveness of the current GBM therapy, diverse natural compounds have been evaluated as chemotherapeutic agents, for example, resveratrol, curcumin, epigallocatechin 3-gallate gallate (EGCC), and others
Sinn et al [22] showed that caffeine can sensitize radiation-resistant cells (U87MG, T98G, and U373MG), due to the activation of the checkpoint in the G1 phase. This effect may be explained by the capability of caffeine to inhibit phosphoinositide 3-kinase (PI3K), down-regulating the PI3K/Akt pathway and inducing apoptosis
Summary
Glioblastoma (GBM) is the most aggressive and most frequent primary malignant tumor of the central nervous system (CNS) [1]. Due to the ineffectiveness of the current GBM therapy, diverse natural compounds have been evaluated as chemotherapeutic agents, for example, resveratrol, curcumin, epigallocatechin 3-gallate gallate (EGCC), and others These agents can be used as adjuvant therapy to improve standard treatments [8]. The EGCC in green tea induces cell death and reduces cellular proliferation and invasion in diverse glioma cell lines It enhances the efficacy of chemotherapy and radiotherapy in GBM [10]. There are several natural or synthetic compounds that inhibit the activity of PDEs, such as MXTs, which are natural PDE-inhibitors and are currently used as therapy for several non-neoplastic diseases, with adequate pharmacokinetic, pharmacodynamic, and security profiles [11] Due to their pharmacological properties, MXTs could become an adjuvant therapy against GBM [12,13]. We will discuss the current status of natural MXTs as therapy for GBM in vitro and in vivo (Figure 1)
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