TRAIL-Induced Apoptosis in TRAIL-Resistant Breast Carcinoma Through Quercetin Cotreatment

Manouchehri, Jasmine M.; Turner, Katherine A.; Kalafatis, Michael

doi:10.1177/1178223417749855

Cited by 21 publications

(34 citation statements)

References 44 publications

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“…Targeting of rG4 regulated pathways is an emerging area of therapeutic potential for fighting cancer 40,41 and sensitization of TRAIL-resistant breast carcinoma to TRAIL mediated apoptosis is a current therapeutic target 27,29,30 . Our data underline the potential for the integration of rG4 therapeutics with an existing cancer treatment interest.…”

Section: Discussionmentioning

confidence: 99%

“…TRAIL resistance occurs in breast cancer cells when the death receptors DR4 and DR5 (TRAIL-R2) are no longer expressed on the cell surface 28 . TRAIL sensitization is emerging as a novel therapeutic target for treating resistance breast cancers 29,30 . We confirm by qPCR and Western blot that regulation of MAGED2 by DDX21 also affects the downstream target of MAGED2, TRAIL-R2, and imparts a sensitivity to TRAIL mediated apoptosis.…”

Section: Introductionmentioning

confidence: 99%

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An RNA guanine quadruplex regulated pathway to TRAIL-sensitization by DDX21

McRae

Dupas

Booy

et al. 2019

Preprint

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DDX21 is a newly discovered RNA G-quadruplex (rG4) binding protein with no known biological rG4 targets. In this study we identified 26 proteins that are expressed at significantly different levels in cells expressing wild type DDX21 relative to an rG4 binding deficient DDX21 (M4). From this list we validate MAGED2 as a protein that is regulated by DDX21 through rG4 in its 5'UTR. MAGED2 protein levels, but not mRNA levels, are reduced by half in cells expressing only DDX21 M4. MAGED2 has a repressive effect on TRAIL-R2 expression that is relieved under these conditions, resulting in elevated TRAIL-R2 mRNA and protein in cells expressing only DDX21 M4, and rendering previously resistant cells sensitive to TRAIL mediated apoptosis. Our work identifies the role of DDX21 in regulation at the translational level through biologically relevant rG4 and shows that MAGED2 protein levels are regulated, at least in part, by a rG4 forming potential in their 5'UTRs.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

An RNA guanine quadruplex regulated pathway to TRAIL-sensitization by DDX21

McRae

Dupas

Booy

et al. 2019

Preprint

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“…Quercetin treatment sensitized recombinant human TRAIL (rhTRAIL) resistant BT-20 TNBC cells to rhTRAIL induced apoptosis [ 230 ]. Quercetin treatment remodels the tumor microenvironment and thus improves the permeation, retention, and antitumor effects of nanoparticles [ 231 ].…”

Section: Phytochemicals As Anticancer Compounds Effective In the Tmentioning

confidence: 99%

The “Yin and Yang” of Natural Compounds in Anticancer Therapy of Triple-Negative Breast Cancers

Varghese

Samuel

Abotaleb

et al. 2018

Cancers

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Among the different types of breast cancers, triple-negative breast cancers (TNBCs) are highly aggressive, do not respond to conventional hormonal/human epidermal growth factor receptor 2 (HER2)-targeted interventions due to the lack of the respective receptor targets, have chances of early recurrence, metastasize, tend to be more invasive in nature, and develop drug resistance. The global burden of TNBCs is increasing regardless of the number of cytotoxic drugs being introduced into the market each year as they have only moderate efficacy and/or unforeseen side effects. Therefore, the demand for more efficient therapeutic interventions, with reduced side effects, for the treatment of TNBCs is rising. While some plant metabolites/derivatives actually induce the risk of cancers, many plant-derived active principles have gained attention as efficient anticancer agents against TNBCs, with fewer adverse side effects. Here we discuss the possible oncogenic molecular pathways in TNBCs and how the purified plant-derived natural compounds specifically target and modulate the genes and/or proteins involved in these aberrant pathways to exhibit their anticancer potential. We have linked the anticancer potential of plant-derived natural compounds (luteolin, chalcones, piperine, deguelin, quercetin, rutin, fisetin, curcumin, resveratrol, and others) to their ability to target multiple dysregulated signaling pathways (such as the Wnt/β-catenin, Notch, NF-κB, PI3K/Akt/mammalian target of rapamycin (mTOR), mitogen-activated protein kinase (MAPK) and Hedgehog) leading to suppression of cell growth, proliferation, migration, inflammation, angiogenesis, epithelial-mesenchymal transition (EMT) and metastasis, and activation of apoptosis in TNBCs. Plant-derived compounds in combination with classical chemotherapeutic agents were more efficient in the treatment of TNBCs, possibly with lesser side effects.

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“…33 Oncolytic adenovirus expressing TRAIL in combination with quercetin effectively induced apoptosis in SMMC-7721, HepG2, and HuH-7 cells. 33 Oncolytic adenovirus expressing TRAIL in combination with quercetin effectively induced apoptosis in SMMC-7721, HepG2, and HuH-7 cells.…”

Section: Quercetin As a Trailmentioning

confidence: 99%

“…Quercetin effectively sensitized TRAIL-resistant breast cancer cells to recombinant human TRAIL-mediated apoptosis through the proteasome-induced degradation of long isoform of c-FLIP and the transcriptional upregulation of DR5. 33 Oncolytic adenovirus expressing TRAIL in combination with quercetin effectively induced apoptosis in SMMC-7721, HepG2, and HuH-7 cells. 34 Expression levels of IκBα, p65, and p50 were significantly reduced in cancer cells combinatorially treated with quercetin and ZD55-TRAIL as compared with cells treated only with ZD55-TRAIL.…”

Section: Quercetin As a Trailmentioning

confidence: 99%

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

Farooqı

Jabeen

Attar

et al. 2018

J of Cellular Biochemistry

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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.

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TRAIL-Induced Apoptosis in TRAIL-Resistant Breast Carcinoma Through Quercetin Cotreatment

Cited by 21 publications

References 44 publications

An RNA guanine quadruplex regulated pathway to TRAIL-sensitization by DDX21

An RNA guanine quadruplex regulated pathway to TRAIL-sensitization by DDX21

The “Yin and Yang” of Natural Compounds in Anticancer Therapy of Triple-Negative Breast Cancers

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

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