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      Therapeutic perspective of thymoquinone: A mechanistic treatise

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          Abstract

          The higher utilization of fruits and vegetables is well known to cure human maladies due to the presence of bioactive components. Among these compounds, thymoquinone, a monoterpene and significant constituent in the essential oil of Nigella sativa L., has attained attention by the researchers due to their pharmacologies perspectives such as prevention from cancer, antidiabetic and antiobesity, prevention from oxidative stress and cardioprotective disorder. Thymoquinone has been found to work as anticancer agent against different human and animal cancer stages including propagation, migration, and invasion. Thymoquinone as phytochemical also downregulated the Rac1 expression, mediated the miR‐34a upregulation, and increased the levels of miR‐34a through p53, as well as also regulated the pro‐ and antiapoptotic genes and decreased the phosphorylation of NF‐κB and IKKα/β. In addition, thymoquinone also lowered the metastasis and ERK1/2 and PI3K activities. The present review article has been piled by adapting narrative review method and highlights the diverse aspects of thymoquinone such as hepatoprotective, anti‐inflammatory, and antiaging through various pathways, and further utilization of this compound in diet has been proven effective against different types of cancers.

          Abstract

          Thymoquinone is strong anticancer agent through multiple mechanistic routes.

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          Most cited references134

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          Targeting the STAT3 signaling pathway in cancer: role of synthetic and natural inhibitors.

          Signal transducers and activators of transcription (STATs) comprise a family of cytoplasmic transcription factors that mediate intracellular signaling that is usually generated at cell surface receptors and thereby transmit it to the nucleus. Numerous studies have demonstrated constitutive activation of STAT3 in a wide variety of human tumors, including hematological malignancies (leukemias, lymphomas, and multiple myeloma) as well as diverse solid tumors (such as head and neck, breast, lung, gastric, hepatocellular, colorectal and prostate cancers). There is strong evidence to suggest that aberrant STAT3 signaling promotes initiation and progression of human cancers by either inhibiting apoptosis or inducing cell proliferation, angiogenesis, invasion, and metastasis. Suppression of STAT3 activation results in the induction of apoptosis in tumor cells, and accordingly its pharmacological modulation by tyrosine kinase inhibitors, antisense oligonucleotides, decoy nucleotides, dominant negative proteins, RNA interference and chemopreventive agents have been employed to suppress the proliferation of various human cancer cells in culture and tumorigenicity in vivo. However, the identification and development of novel drugs that can target deregulated STAT3 activation effectively remains an important scientific and clinical challenge. This review presents the evidence for critical roles of STAT3 in oncogenesis and discusses the potential for development of novel cancer therapies based on mechanistic understanding of STAT3 signaling cascade. Copyright © 2013 Elsevier B.V. All rights reserved.
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            Punctuated Copy Number Evolution and Clonal Stasis in Triple-Negative Breast Cancer

            Aneuploidy is a hallmark of breast cancer; however, our knowledge of how these complex genomic rearrangements evolve during tumorigenesis is limited. In this study we developed a highly multiplexed single-nucleus-sequencing method to investigate copy number evolution in triple-negative breast cancer patients. We sequenced 1000 single cells from 12 patients and identified 1–3 major clonal subpopulations in each tumor that shared a common evolutionary lineage. We also identified a minor subpopulation of non-clonal cells that were classified as: 1) metastable, 2) pseudo-diploid, or 3) chromazemic. Phylogenetic analysis and mathematical modeling suggest that these data are unlikely to be explained by the gradual accumulation of copy number events over time. In contrast, our data challenge the paradigm of gradual evolution, showing that the majority of copy number aberrations are acquired at the earliest stages of tumor evolution, in short punctuated bursts, followed by stable clonal expansions that form the tumor mass.
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              Targeting nuclear factor-kappa B activation pathway by thymoquinone: role in suppression of antiapoptotic gene products and enhancement of apoptosis.

              Thymoquinone (TQ), derived from the medicinal plant Nigella sativa, exhibits antiinflammatory and anticancer activities through mechanism(s) that is not fully understood. Because numerous effects modulated by TQ can be linked to interference with the nuclear factor-kappaB (NF-kappa B) signaling, we investigated in detail the effect of this quinone on NF-kappa B pathway. As examined by DNA binding, we found that TQ suppressed tumor necrosis factor-induced NF-kappa B activation in a dose- and time-dependent manner and inhibited NF-kappaB activation induced by various carcinogens and inflammatory stimuli. The suppression of NF-kappaB activation correlated with sequential inhibition of the activation of I kappa B alpha kinase, I kappa B alpha phosphorylation, I kappa B alpha degradation, p65 phosphorylation, p65 nuclear translocation, and the NF-kappa B-dependent reporter gene expression. TQ specifically suppressed the direct binding of nuclear p65 and recombinant p65 to the DNA, and this binding was reversed by DTT. However, TQ did not inhibit p65 binding to DNA when cells were transfected with the p65 plasmid containing cysteine residue 38 mutated to serine. TQ also down-regulated the expression of NF-kappa B-regulated antiapoptotic (IAP1, IAP2, XIAP Bcl-2, Bcl-xL, and survivin), proliferative (cyclin D1, cyclooxygenase-2, and c-Myc), and angiogenic (matrix metalloproteinase-9 and vascular endothelial growth factor) gene products. This led to potentiation of apoptosis induced by tumor necrosis factor and chemotherapeutic agents. Overall, our results indicate that the anticancer and antiinflammatory activities previously assigned to TQ may be mediated in part through the suppression of the NF-kappa B activation pathway, as shown here, and thus may have potential in treatment of myeloid leukemia and other cancers.
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                Author and article information

                Contributors
                f.saeed@gcuf.edu.pk
                saifulinfs@du.ac.bd
                Journal
                Food Sci Nutr
                Food Sci Nutr
                10.1002/(ISSN)2048-7177
                FSN3
                Food Science & Nutrition
                John Wiley and Sons Inc. (Hoboken )
                2048-7177
                28 January 2021
                March 2021
                : 9
                : 3 ( doiID: 10.1002/fsn3.v9.3 )
                : 1792-1809
                Affiliations
                [ 1 ] Faculty of Food, Nutrition & Home Sciences National Institute of Food Science and Technology UAF Faisalabad Pakistan
                [ 2 ] Faculty of Allied Health Sciences University Institute of Diet and Nutritional Sciences The University of Lahore Lahore Pakistan
                [ 3 ] Department of Food Science Institute of Home and Food Sciences Government College University Faisalabad Pakistan
                [ 4 ] School of Exercise and Nutrition Faculty of Health Deakin University Burwood Vic. Australia
                [ 5 ] Food Engineering Department Shakarim State University of Semey Semey Kazakhstan
                [ 6 ] Department of Dairy Technology University of Veterinary and Animal Sciences Lahore Pakistan
                [ 7 ] Department of molecular Biology and Genetics Shaheed Benazir Bhutto University Shaheed Benazirabad Pakistan
                [ 8 ] Department of Health Sciences Faculty of Medicine and Health Sciences University of Mauritius Réduit Mauritius
                [ 9 ] Institute of Nutrition and Food Science University of Dhaka Dhaka Bangladesh
                [ 10 ] School of life Sciences Forman Christian College (A Chartered University) Lahore Pakistan
                Author notes
                [*] [* ] Correspondence

                Farhan Saeed, Department of Food Science, Institute of Home and Food Sciences, Government College University, Faisalabad, Pakistan.

                Email f.saeed@ 123456gcuf.edu.pk

                Saiful Islam, Institute of Nutrition and Food Science, University of Dhaka, Dhaka, Bangladesh.

                Email: saifulinfs@ 123456du.ac.bd

                Author information
                https://orcid.org/0000-0001-9564-886X
                https://orcid.org/0000-0001-5340-4015
                https://orcid.org/0000-0002-1117-3703
                https://orcid.org/0000-0003-3962-8666
                Article
                FSN32070
                10.1002/fsn3.2070
                7958532
                671b96ab-6711-4a78-a331-c075e35217db
                © 2021 The Authors. Food Science & Nutrition published by Wiley Periodicals LLC

                This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                : 02 November 2020
                : 16 July 2020
                : 03 December 2020
                Page count
                Figures: 3, Tables: 1, Pages: 0, Words: 13513
                Funding
                Funded by: The Higher Education Commission of Pakistan
                Categories
                Review
                Reviews
                Custom metadata
                2.0
                March 2021
                Converter:WILEY_ML3GV2_TO_JATSPMC version:5.9.9 mode:remove_FC converted:15.03.2021

                anticancer,antioxidant potential,cardioprotective disorder,phytochemical,thymoquinone

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