The Role of Natural Products as Inhibitors of JAK/STAT Signaling Pathways in Glioblastoma Treatment

Abstract

The permeability of glioblastoma, as well as its escaping the immune system, makes them one of the most deadly human malignancies. By avoiding programmed cell death (apoptosis), unlimited cell growth and metastatic ability could dramatically affect the immune system. Genetic mutations, epigenetic changes, and overexpression of oncogenes can cause this process. On the other hand, the blood-brain barrier (BBB) and intratumor heterogeneity are important factors causing resistance to therapy. Several signaling pathways have been identified in this field, including the Janus tyrosine kinase (JAK) converter and signal transducer and activator of transcription (STAT) activator pathways, which are closely related. In addition, the JAK/STAT signaling pathway contributes to a wide array of tumorigenesis functions, including replication, anti-apoptosis, angiogenesis, and immune suppression. Introducing this pathway as the main tumorigenesis and treatment resistance center can give a better understanding of how it operates. In light of this, it is an important goal in treating many disorders, particularly cancer. The inhibition of this signaling pathway is being considered an approach to the treatment of glioblastoma. The use of natural products alternatively to conventional therapies is another area of research interest among researchers. Some natural products that originate from plants or natural sources can interfere with JAK/STAT signaling in human malignant cells, also by stopping the progression and phosphorylation of JAK/STAT, inducing apoptosis, and stopping the cell cycle. Natural products are a viable alternative to conventional chemotherapy because of their cost-effectiveness, wide availability, and almost no side effects.

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“…Thus, targeting the miRNAs via polyphenols was planned as a novel and potential approach to antitumor chemotherapy. By preventing NF-κB activation, polyphenols repress the expression of diverse cell survival and proliferative genes. , Phytochemicals significantly stimulate cell death in several cancers by preventing the activity of the JAK/STAT pathway and activating apoptosis, which stimulates cell death by preventing constituent activation of STAT3 and decreasing regulating survivin and Mcl-1. , Phytochemicals inhibit the translocation and accretion of β-catenin in the nucleus by activating GSK3 …”