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Review
. 2020 Jun 11;9(6):1451.
doi: 10.3390/cells9061451.

Targeting the JAK/STAT Signaling Pathway Using Phytocompounds for Cancer Prevention and Therapy

Sankhadip Bose  1 , Sabyasachi Banerjee  2 , Arijit Mondal  3 , Utsab Chakraborty  2 , Joshua Pumarol  4 , Courtney R Croley  4 , Anupam Bishayee  4
Affiliations
Review

Targeting the JAK/STAT Signaling Pathway Using Phytocompounds for Cancer Prevention and Therapy

Sankhadip Bose et al. Cells. .

Abstract

Cancer is a prevalent cause of mortality around the world. Aberrated activation of Janus kinase (JAK)/signal transducer and activator of transcription (STAT) signaling pathway promotes tumorigenesis. Natural agents, including phytochemicals, exhibit potent anticancer activities via various mechanisms. However, the therapeutic potency of phytoconstituents as inhibitors of JAK/STAT signaling against cancer has only come into focus in recent days. The current review highlights phytochemicals that can suppress the JAK/STAT pathway in order to impede cancer cell growth. Various databases, such as PubMed, ScienceDirect, Web of Science, SpringerLink, Scopus, and Google Scholar, were searched using relevant keywords. Once the authors were in agreement regarding the suitability of a study, a full-length form of the relevant article was obtained, and the information was gathered and cited. All the complete articles that were incorporated after the literature collection rejection criteria were applied were perused in-depth and material was extracted based on the importance, relevance, and advancement of the apprehending of the JAK/STAT pathway and their relation to phytochemicals. Based on the critical and comprehensive analysis of literature presented in this review, phytochemicals from diverse plant origins exert therapeutic and cancer preventive effects, at least in part, through regulation of the JAK/STAT pathway. Nevertheless, more preclinical and clinical research is necessary to completely comprehend the capability of modulating JAK/STAT signaling to achieve efficient cancer control and treatment.

Keywords: Janus kinase; cancer; natural compounds; signal transducer and activator of transcription; targeted therapy.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Schematic representation of Janus kinase (JAK)/signal transducer and activator of transcription (STAT) signaling pathway activation leading to upregulation of genes involved in survival and tumor cell proliferation. Various steps in the JAK/STAT pathway: I: Cytokine binds to receptor and receptors dimerize. II: JAKs are phosphorylated by each other. III: JAK phosphorylates the receptor, forming phosphotyrosine binding sites for STAT’s SH2 domain. IV: STAT binds to the receptor. JAK phosphorylates STAT which changes the conformation of STAT and stimulates its release. V: Phosphorylated STAT dissociates from the receptor and dimerizes. VI: Phosphorylated STAT translocates into the nucleus. VII. Phosphorylated STAT binds to DNA. VIII. Stimulation of DNA transcription of target genes.
Figure 2
Figure 2
Structures of phenolics and polyphenols with anticancer activities correlated with inhibition of the JAK/STAT pathway.
Figure 3
Figure 3
Structures of the terpenoids with anticancer activities related to inhibition of the JAK/STAT pathwa.
Figure 4
Figure 4
Structures of alkaloids, saponins, and steroids involved in anticancer activities related to inhibition of the JAK/STAT pathway.
Figure 5
Figure 5
Illustration of various phytochemicals blocking specific steps in the JAK/STAT signaling pathway in relation to their cancer preventive and anticancer actions.
See this image and copyright information in PMC

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