Quercetin‐mediated regulation of signal transduction cascades and microRNAs: Natural weapon against cancer

Abstract

Recent technological and analytical breakthroughs in genomics and proteomics have deepened our understanding related to the multifaceted nature of cancer. Because of therapeutically challenging nature of cancer, there has been a renewed interest in phytochemistry, and much attention is currently being given to the identification of signaling pathway inhibitors. Data obtained through high-throughput technologies has provided a broader landscape of wiring maps of complex oncogenic signaling networks, thus revealing novel therapeutic opportunities. Increasingly, it is being realized that although our knowledge related to physiological and pathophysiological roles of signal transduction cascades has evolved rapidly, the clinical development of signaling pathway inhibitors has been challenging. Quercetin has attracted considerable attention because of its amazingly high pharmacological value. Research over decades has sequentially shown that quercetin effectively inhibited cancer development and progression. In this review, we have attempted to set the spotlight on the regulation of different cell signaling pathways by quercetin. We partition this multicomponent review into how quercetin effectively regulates the Wnt/β-catenin pathway, Janus kinase-signal transducer and activator of transcription pathway, and vascular endothelial growth factor/vascular endothelial growth factor receptor signaling cascade in different types of cancers. We also provide an overview of the regulation of NOTCH and SHH pathways by quercetin. MicroRNAs (miRNAs) have also emerged as versatile regulators of cancer, and contemporary studies have shed light on the ability of quercetin to control different miRNAs in various cancers. We have scattered information related to NOTCH and SHH pathways, and future studies must converge on the investigation of these pathways to see how quercetin modulates the signaling machinery of these pathways.

Quercetin and MicroRNA Interplay in Apoptosis Regulation in Ovarian Cancer

“…Its anti-inflammatory, anti-proliferative, anti-aging, cardio-protective and anti-carcinogenic properties are well documented, and it is regarded as a natural bioactive compound with profound pharmacological implications [14][15][16]. It has been reported that quercetin modulates the expression of various intracellular pathways such as those controlled by Wnt- catenin, Janus Kinase (JAK) and signal transducer and activator of transcription (STAT), and also vascular endothelial growth factor/vascular endothelial growth factor receptor (VEGF/VEGFR), and epidermal growth factor (EGF)/epidermal growth factor receptor (EGFR) signaling cascades in different types of cancers [9]. This review summarizes the recent development of knowledge on TRAIL, quercetin and their interplay with oncogenic and tumor suppressor microRNAs (miRNAs) involved in mediating apoptosis in ovarian cancer.…”

“…Significant reduction in malignant transformation of BEAS-2B cells was observed by miR-21 knockdown. Furthermore, in PDCD4-overexpressing BEAS-2Bcells, the extent of hexavalent chromium-mediated malignant transformation was considerably decreased[9].…”

The modulatory properties of Astragalus membranaceus treatment on endometrial cancer: an integrated pharmacological method

“…Quercetin is one of the most important flavonoids in the human diet ( Lin et al, 2017 ). Quercetin has attracted considerable attention because of its amazing anti-cancer properties, such as cell signalling, pro-apoptosis, anti-proliferative and anti-oxidant effects, and growth inhibition ( Farooqi et al, 2018 ). In fact, the ability of quercetin to inhibit the action of multiple enzymes involved in cell proliferation and multiple signal transduction pathways in endometrial cancer has been established ( Kaneuchi et al, 2003 ; Scambia et al, 1992 ; Wang et al, 2009 ).…”

Riddle of the Sphinx: Emerging Role of Transfer RNAs in Human Cancer

“…Cancer is one of the most complex diseases caused by multiple genetic disorders and cellular abnormalities. Its development and progression are regulated by multiple pathological processes ( Bhawe and Roy, 2018 ), including environmental ( Pan et al, 2018 ; Lewandowska et al, 2019 ), gender ( Jara-Palomares et al, 2018 ), cultural ( Tejeda et al, 2017 ; Lee, 2018 ), and lifestyle factors ( Kerr et al, 2017 ; Jara-Palomares et al, 2018 ), as well as genetic mutations ( Pak et al, 2015 ; Tejeda et al, 2017 ; Liew et al, 2019 ), epigenetic changes ( Zhang and Huang, 2017 ; Porcellini et al, 2018 ; Liew et al, 2019 ), and abnormal signal transduction ( Farooqi et al, 2018 ). Tremendous efforts have been made over the past decades with the aim of searching novel and more efficient tools in cancer therapy ( Winn et al, 2016 ).…”