Luteolin mediated targeting of protein network and microRNAs in different cancers: Focus on JAK-STAT, NOTCH, mTOR and TRAIL-mediated signaling pathways. (October 2020)

• Record Type: Journal Article
• Authors: Farooqi, Ammad Ahmad; Butt, Ghazala; El-Zahaby, Sally A.; Attar, Rukset; Sabitaliyevich, Uteuliyev Yerzhan; Jovic, Jovana Joksimovic; Tang, Kai-Fu; Naureen, Humaira; Xu, Baojun
• Is Part Of: Pharmacological research. Volume 160(2020)
• Publication Date: 2020-10
• Subjects: Luteolin (PubChem CID: 5280445) -- Luteolin-7-O-glucuronide (PubChem CID: 13607752) -- Luteolin-3'-O-glucuronide (PubChem CID: 10253785) -- Diosmetin (PubChem CID: 5281612) -- Chrysoeriol (PubChem CID: 5280666); JAKs Janus kinases -- STAT signal transducers and activators of transcriptions -- TH1 T helper type 1 -- CFH complement factor H -- SOCS suppressor of cytokine signaling -- MLC monocyte lineage cell -- mTAMs metastatic TAMs -- SHP-2 Src homology domain 2 containing tyrosine phosphatase-2 -- S100A7 S100 calcium-binding protein A7 -- EMT epithelial-mesenchymal transition -- NICD NOTCH intracellular fragment -- VEGF vascular endothelial growth factor -- HUVECs human umbilical vein endothelial cells -- RSK p90 ribosomal S6 kinase -- YB-1 Y-box binding protein-1 -- TRAIL TNF-related apoptosis-inducing ligand -- JNK c-Jun N-terminal kinase -- XIAP X-linked inhibitor of apoptosis protein -- DRPs dynamin-related proteins -- DISC death inducing signaling complex -- EGFR epidermal growth factor receptor -- MLL3 mixed-lineage leukemia 3 -- miRNAs microRNAs -- HK1 hexokinase 1 -- MDM4 mouse double minute 4 Homolog -- GAK cyclin G-associated kinase -- DEDD2 death effector domain-containing protein 2 -- AIM2 absent in melanoma 2 -- dsDNA double‐stranded DNAPDTX patient-derived human tumor xenograft -- UGTs UDP-glucuronosyltransferases -- OATPs organic anion transporters -- COMT catechol-O-methyltransferase -- MMP-2 metalloproteinase-2; Luteolin -- Cancer therapy -- Signaling pathways -- microRNAs; Pharmacology -- Periodicals; Pharmacology -- Periodicals; Research -- Periodicals; Médicaments -- Recherche -- Périodiques; Pharmacologie -- Périodiques; 615.105
• DOI: 10.1016/j.phrs.2020.105188
• Languages: English
• ISSNs: 1043-6618

Abstract

Abstract: There has always been a keen interest of basic and clinical researchers to search for cancer therapeutics having minimum off-target effects and maximum anticancer activities. In accordance with this approach, there has been an explosion in the field of natural products research in the past few decades because of extra-ordinary list of natural extracts and their biologically and pharmacologically active constituents having significant medicinal properties. Apparently, luteolin-mediated anticancer effects have been investigated in different cancers but there is superfluousness of superficial data. Generalized scientific evidence encompassing apoptosis, DNA damage and anti-inflammatory effects has been reported extensively. However, how luteolin modulates deregulated oncogenic pathways in different cancers has not been comprehensively uncovered. In this review we have attempted to focus on cutting-edge research which has unveiled remarkable abilities of luteolin to modulate deregulated oncogenic pathways in different cancers. We have partitioned the review into various sections to separately discuss advancements in therapeutic targeting of oncogenic protein networks. We have provided detailed mechanistic insights related to JAK-STAT signaling and summarized how luteolin inhibited STAT proteins to inhibit STAT-driven gene network. We have also individually analyzed Wnt/β-catenin and NOTCH pathway and how luteolin effectively targeted these pathways. Mapping of the signaling landscape has revealed that NOTCH pathway can be targeted therapeutically. NOTCH pathway was noted to be targeted by luteolin. We have also conceptually analyzed how luteolin restored TRAIL-induced apoptosis in resistant cancers. Luteolin induced an increase in pro-apoptotic proteins and efficiently inhibited anti-apoptotic proteins to induce apoptosis. Luteolin mediated regulation of non-coding RNAs is an exciting and emerging facet. Excitingly, there is sequential and systematic accumulation of clues which have started to shed light on intricate regulation of microRNAs by luteolin in different cancers. Collectively, sophisticated information will enable us to develop a refined understanding of the multi-layered regulation of signaling pathways and non-coding RNAs by luteolin in different cancers.