Targeting kinases with thymoquinone: a molecular approach to cancer therapeutics

Afrose, Syeda Samira; Junaid, Md.; Akter, Yeasmin; Tania, Mousumi; Zheng, Meiling; Khan, Md. Asaduzzaman

doi:10.1016/j.drudis.2020.07.019

Cited by 26 publications

(19 citation statements)

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“…Kinases are cellular enzyme stimuli, essential for cellular metabolic functions, and their overexpression is closely linked with cancer [ 73 ]. TQ effectively targets many phosphoinositides, including 3-kinase (PI3K) [ 74 ], mitogen-activated protein kinase (MAPK)/Janus kinase signal transducers and transcription (JAK/STAT) [ 75 , 76 ], polo-like kinase 1 (PLC1) [ 77 ] and tyrosine kinase [ 78 ].…”

Section: Neoplasm and Its Pathogenesismentioning

confidence: 99%

“…TQ-NLC-NPs accumulated in cancer cells and inhibited their proliferation through time and dose-dependent modulation in the cellular morphology, as investigated in HepG2 cancer cells [ 182 ]. The polymeric NPs of methoxy poly(ethylene glycol)-b-poly(-caprolactone) improved the systemic bioavailability of TQ (1.3-fold) with slower elimination rates, which provides greater antiproliferative efficacy against varieties of pure cell cultures of human carcinoma (PANC-1, MCF-7, and Caco-2) [ 78 , 183 ]. The nanoarchitecture of polymeric shells increased TQ solubility, intestinal absorption, and bioavailability rates, resulting in higher cancer cell selectivity compared to free TQ.…”

Section: Neoplasm and Its Pathogenesismentioning

confidence: 99%

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Recent Findings on Thymoquinone and Its Applications as a Nanocarrier for the Treatment of Cancer and Rheumatoid Arthritis

et al. 2021

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Cancer causes a considerable amount of mortality in the world, while arthritis is an immunological dysregulation with multifactorial pathogenesis including genetic and environmental defects. Both conditions have inflammation as a part of their pathogenesis. Resistance to anticancer and disease-modifying antirheumatic drugs (DMARDs) happens frequently through the generation of energy-dependent transporters, which lead to the expulsion of cellular drug contents. Thymoquinone (TQ) is a bioactive molecule with anticancer as well as anti-inflammatory activities via the downregulation of several chemokines and cytokines. Nevertheless, the pharmacological importance and therapeutic feasibility of thymoquinone are underutilized due to intrinsic pharmacokinetics, including short half-life, inadequate biological stability, poor aqueous solubility, and low bioavailability. Owing to these pharmacokinetic limitations of TQ, nanoformulations have gained remarkable attention in recent years. Therefore, this compilation intends to critically analyze recent advancements in rheumatoid arthritis and cancer delivery of TQ. This literature search revealed that nanocarriers exhibit potential results in achieving targetability, maximizing drug internalization, as well as enhancing the anti-inflammatory and anticancer efficacy of TQ. Additionally, TQ-NPs (thymoquinone nanoparticles) as a therapeutic payload modulated autophagy as well as enhanced the potential of other drugs when given in combination. Moreover, nanoformulations improved pharmacokinetics, drug deposition, using EPR (enhanced permeability and retention) and receptor-mediated delivery, and enhanced anti-inflammatory and anticancer properties. TQ’s potential to reduce metal toxicity, its clinical trials and patents have also been discussed.

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Section: Neoplasm and Its Pathogenesismentioning

confidence: 99%

Section: Neoplasm and Its Pathogenesismentioning

confidence: 99%

Recent Findings on Thymoquinone and Its Applications as a Nanocarrier for the Treatment of Cancer and Rheumatoid Arthritis

et al. 2021

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“…It has been subject of repeated studies evaluating its chemopreventive and anticancer effects [ 209 ]. Thereby, thymoquinone was targeting a variety of kinases and additionally showed effectiveness in murine tumor models [ 210 , 211 ]. In order to evaluate its antimyeloma potential, the compound was investigated for its antiproliferative effect on U266 and RPMI8226 cells, with IC 50 values below 10 µM after 12 h of incubation [ 208 ].…”

Section: Resultsmentioning

confidence: 99%

Multiple Myeloma Inhibitory Activity of Plant Natural Products

Jöhrer

Ҫiҫek

2021

Cancers

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A literature search on plant natural products with antimyeloma activity until the end of 2020 resulted in 92 compounds with effects on at least one human myeloma cell line. Compounds were divided in different compound classes and both their structure–activity-relationships as well as eventual correlations with the pathways described for Multiple Myeloma were discussed. Each of the major compound classes in this review (alkaloids, phenolics, terpenes) revealed interesting candidates, such as dioncophyllines, a group of naphtylisoquinoline alkaloids, which showed pronounced and selective induction of apoptosis when substituted in position 7 of the isoquinoline moiety. Interestingly, out of the phenolic compound class, two of the most noteworthy constituents belong to the relatively small subclass of xanthones, rendering this group a good starting point for possible further drug development. The class of terpenoids also provides noteworthy constituents, such as the highly oxygenated diterpenoid oridonin, which exhibited antiproliferative effects equal to those of bortezomib on RPMI8226 cells. Moreover, triterpenoids containing a lactone ring and/or quinone-like substructures, e.g., bruceantin, whitaferin A, withanolide F, celastrol, and pristimerin, displayed remarkable activity, with the latter two compounds acting as inhibitors of both NF-κB and proteasome chymotrypsin-like activity.

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“…eEF-2 K is affiliated to the Ca 2+ /CaM-dependent α-kinase family. eEF-2 K can phosphorylate and consequently inactivate eEF-2 (at Thr56) and eventually prevent peptide chains from attaining enough elongation within mRNA translation [ 72 , 73 ]. Recent investigations have shown that eEF-2 K is a significant signal transduction factor interfering in the most devastating cancers such as pancreatic, glioblastoma and breast cancers [ 74 , 75 ].…”

Section: Thymoquinone Effects On Mirna Regulation In Signaling Pathwaysmentioning

confidence: 99%

Targeting microRNAs with thymoquinone: a new approach for cancer therapy

2021

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Cancer is a global disease involving transformation of normal cells into tumor types via numerous mechanisms, with mortality among all generations, in spite of the breakthroughs in chemotherapy, radiotherapy and/or surgery for cancer treatment. Since one in six deaths is due to cancer, it is one of the overriding priorities of world health. Recently, bioactive natural compounds have been widely recognized due to their therapeutic effects for treatment of various chronic disorders, notably cancer. Thymoquinone (TQ), the most valuable constituent of black cumin seeds, has shown anti-cancer characteristics in a wide range of animal models. The revolutionary findings have revealed TQ’s ability to regulate microRNA (miRNA) expression, offering a promising approach for cancer therapy. MiRNAs are small noncoding RNAs that modulate gene expression by means of variation in features of mRNA. MiRNAs manage several biological processes including gene expression and cellular signaling pathways. Accordingly, miRNAs can be considered as hallmarks for cancer diagnosis, prognosis and therapy. The purpose of this study was to review the various molecular mechanisms by which TQ exerts its potential as an anti-cancer agent through modulating miRNAs.

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Targeting kinases with thymoquinone: a molecular approach to cancer therapeutics

Cited by 26 publications

References 235 publications

Recent Findings on Thymoquinone and Its Applications as a Nanocarrier for the Treatment of Cancer and Rheumatoid Arthritis

Recent Findings on Thymoquinone and Its Applications as a Nanocarrier for the Treatment of Cancer and Rheumatoid Arthritis

Multiple Myeloma Inhibitory Activity of Plant Natural Products

Targeting microRNAs with thymoquinone: a new approach for cancer therapy

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