There has been a renewed interest in the identification of natural products having premium pharmacological properties and minimum off-target effects. In accordance with this approach, natural product research has experienced an exponential growth in the past two decades and has yielded a stream of preclinical and clinical insights which have deeply improved our knowledge related to the multifaceted nature of cancer and strategies to therapeutically target deregulated signaling pathways in different cancers. In this review, we have set the spotlight on the scientifically proven ability of berberine to effectively target a myriad of deregulated pathways.
MicroRNAs (miRNAs) are short non-coding single-stranded RNAs, which play significant roles in the regulation of a myriad of biological processes. Overwhelmingly increasing high-impact research has also deepened our understanding about the central role of miRNAs in cancer development, metastatic spread, and development of resistance against various drugs. Recent studies have identified miRNAs that regulate RNA expression/processing and posttranscriptional expression of important oncogenes and tumor suppressors. Rapidly emerging experimentally verified data have started to shed light on the significance of miRNAs as biomarkers for diagnostic, prognostic, and monitoring purposes. Next-generation sequencing and DNA microarray technologies have helped us tremendously in the identification of miRNA and mRNA signatures in different cancers and their subtypes on a genome-wide scale. It is being increasing realized that miRNAs have diametrically opposite roles in different cancers. miR-410 is context-dependently involved in positive and negative regulation of cancers. miR-410 negatively regulates BAK1, CETN3, and BRD7 to promote cancer. However, miR-410 effectively targetes c-MET, AGTR1, and SNAIL to suppress cancer. In this review, we will comprehensively summarize most recent evidence available related to the "split personality" of miR-410 in different cancers.
Decades of research have enabled us to develop a better and sharper understanding of multifaceted nature of cancer. Next-generation sequencing technologies have leveraged our existing knowledge related to intra- and inter-tumor heterogeneity to the next level. Functional genomics have opened new horizons to explore deregulated signaling pathways in different cancers. Therapeutic targeting of deregulated oncogenic signaling cascades by products obtained from natural sources has shown promising results. Epigallocatechin-3-gallate (EGCG) has emerged as a distinguished chemopreventive product because of its ability to regulate a myriad of oncogenic signaling pathways. Based on its scientifically approved anticancer activity and encouraging results obtained from preclinical trials, it is also being tested in various phases of clinical trials. A series of clinical trials associated with green tea extracts and EGCG are providing clues about significant potential of EGCG to mechanistically modulate wide ranging signal transduction cascades. In this review, we comprehensively analyzed regulation of JAK/STAT, Wnt/β-catenin, TGF/SMAD, SHH/GLI, NOTCH pathways by EGCG. We also discussed most recent evidence related to the ability of EGCG to modulate non-coding RNAs in different cancers. Methylation of the genome is also a widely studied mechanism and EGCG has been shown to modulate DNA methyltransferases (DNMTs) and protein enhancer of zeste-2 (EZH2) in multiple cancers. Moreover, the use of nanoformulations to increase the bioavailability and thus efficacy of EGCG will be also addressed. Better understanding of the pleiotropic abilities of EGCG to modulate intracellular pathways along with the development of effective EGCG delivery vehicles will be helpful in getting a step closer to individualized medicines.
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