Shahwar, D. | Iqbal, M.J. | Nisa, M.-U. | Todorovska, M. | Attar, Rukset | Sabitaliyevich, U.Y. | Xu, B.

Review | 2019 | International Journal of Molecular Sciences20 ( 8 )

Rapidly developing resistance against different therapeutics is a major stumbling block in the standardization of therapy. Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL)-mediated signaling has emerged as one of the most highly and extensively studied signal transduction cascade that induces apoptosis in cancer cells. Rapidly emerging cutting-edge research has helped us to develop a better understanding of the signaling machinery involved in inducing apoptotic cell death. However, excitingly, cancer cells develop resistance against TRAIL-induced apoptosis through different modes. Loss of cell surface expression . . . of TRAIL receptors and imbalance of stoichiometric ratios of pro- and anti-apoptotic proteins play instrumental roles in rewiring the machinery of cancer cells to develop resistance against TRAIL-based therapeutics. Natural products have shown excellent potential to restore apoptosis in TRAIL-resistant cancer cell lines and in mice xenografted with TRAIL-resistant cancer cells. Significantly refined information has previously been added and continues to enrich the existing pool of knowledge related to the natural-product-mediated upregulation of death receptors, rebalancing of pro- and anti-apoptotic proteins in different cancers. In this mini review, we will set spotlight on the most recently published high-impact research related to underlying mechanisms of TRAIL resistance and how these deregulations can be targeted by natural products to restore TRAIL-mediated apoptosis in different cancers. © 2019 by the authors. Licensee MDPI, Basel, Switzerland Daha fazlası Daha az

Butt, G. | Attar, Rukset | Tabassum, S. | Aras, A. | Qadir, M.I. | Ozbey, U. | Farooqi, A.A.

Review | 2017 | Cellular and Molecular Biology63 ( 12 ) , pp.5 - 10

Interdisciplinary research has revolutionized the field of medicine and we have witnessed exponential increase in the high-impact research in past few decades. However, the road to this burgeoning research field is obstacle-ridden because of intratumor heterogeneity, loss of apoptosis and dysregulation of spatio-temporally controlled signaling pathways. Ground-breaking findings obtained through genetic, genomic and proteomic studies have considerably improved our concepts related to the complexity of protein network and excitingly, discovery of miRNAs has added another layer of intricacy to quantitatively regulated gene networks. In . . . this review, we chronicle the milestone achievements and discuss how Pterostilbenes effectively regulated different cellular pathways. We have provided detailed mechanistic insights related to regulation of JAK-STAT signaling, Notch pathway, Wnt mediated intracellular signaling by pterostilbene. Underlying mechanisms about regulation of PI3K/AKT and MAPK pathways by pterostilbene in different cancers. Regulation of Metastasis-associated protein 1 (MTA1) proteins and Human telomerase reverse transcriptase (hTERT) in cancer cells by pterostilbene. Pterostilbene has also been reported to modulate the expression of various oncogenic and tumor suppressor microRNAs in cancer cells. Better and sharper comprehension of the concepts associated with the modes of action of pterostilbene in different cancers will be useful in identification of cancers which can be efficiently targeted by pterostilbene. © 2017 by the C.M.B. Association Daha fazlası Daha az

Farooqi, A.A. | Adylova, A. | Sabitaliyevich, U.Y. | Attar, Rukset | Sohail, M.I. | Yilmaz, S.

Review | 2020 | Gene737 , pp.5 - 10

There has always been a quest to search for synthetic and natural compounds having premium pharmacological properties and minimum off-target and/or side effects. Therefore, in accordance with this approach, scientists have given special attention to the molecules having remarkable ability to target oncogenic protein network, restore drug sensitivity and induce apoptosis in cancer cells. The mechanisms through which general anesthetics modulated wide-ranging deregulated cell signaling pathways and non-coding RNAs remained unclear. However, rapidly accumulating experimentally verified evidence has started to resolve this long-standing . . . mystery and a knowledge about these important molecular targets has surfaced and how these drugs act at the molecular level is becoming more understandable. In this review we have given special attention to available evidence related to ability of propofol to modulate Wnt/ß-catenin, JAK/STAT and mTOR-driven pathway. Excitingly, great strides have been made in sharpening our concepts related to potential of propofol to modulate non-coding RNAs in different cancers. Collectively, these latest findings offer interesting, unexplored opportunities to target deregulated signaling pathways to induce apoptosis in drug-resistant cancers. © 2020 Elsevier B.V Daha fazlası Daha az

Lin, X. | Khalid, S. | Qureshi, M.Z. | Attar, Rukset | Yaylim, I. | Ucak, I. | Ismail, M.

Review | 2016 | Cellular and Molecular Biology62 ( 14 ) , pp.64 - 68

Increasingly it is being realized that oral cancer arises from genetic/epigenetic mutations, dysregulations of spatio-temporally controlled signal transduction cascades and loss of apoptosis. Epidemiological studies have provided a stronger association between tobacco use (chewed and smoked) and oral cancer. Nevertheless, alcohol has also gained attention as a significant risk factor, having a multiplicative synergistic cancer promoting effect with tobacco. Vascular Endothelial Growth Factor (VEGF) mediated signaling has gained limelight because of its instrumental role in endothelial cell proliferation, survival, invasion, migratio . . .n, chemotaxis of bone marrow (BM)-derived progenitor cells, vasodilation and vascular permeability. In this review we provide most recent updates on involvement of VEGF/VEGFR signaling axis in oral cancer. We partition this multi-component review into different sections and summarize latest advancements related to therapies against VEGF/VEGFR signaling axis and how microRNAs tactfully modulate VEGF and VEGFR in oral cancers. Data obtained through preclinical and clinical studies has revealed that therapeutic benefits associated with VEGF-targeted therapy are complicated in different cancers and involve myriad of mechanisms. A better understanding of VEGF/VEGFR mediated signaling in oral cancers and testing of novel therapeutic agents in preclinical models will prove to be helpful in effective translation of safest drugs from benchtop to the bedside. © 2016 by the C.M.B Daha fazlası Daha az

Lin, X. | Qureshi, M.Z. | Attar, Rukset | Khalid, S. | Tahir, F. | Yaqub, A. | Ismail, M.

Review | 2016 | Cellular and Molecular Biology62 ( 12 ) , pp.129 - 137

In 1960 researchers reported that balanced translocation between chromosomes 22 and 9 resulted in the generation of Philadelphia chromosome. This breakthrough revolutionized our knowledge related to leukemia biology and contemporary studies revealed that chromosomal translocation resulted in the fusion between the 5' segment of BCR gene and 3' segment of the ABL gene to form BCR/ABL fusion gene. Research over the years has progressively and systematically improved our understanding of the genetic and proteomic basis of Leukemia. Genome-wide profiling studies, including genome sequencing and microarray analysis, have helped us in ide . . .ntification of different intracellular signaling cascades that are frequently mutated in Leukemia. We partition this multi-component review into different sections related to biochemical characteristics of BCR-ABL+ cells, underlying mechanism of generation of mutations and crosstalk of BCR-ABL with various intracellular signaling cascades. We also summarize how BCR-ABL encoding mRNA is negatively regulated by different miRNAs and the strategies which are currently being used to effectively target BCR-ABL protein. We also provide an overview of the natural products which have been used for targeting of BCR-ABL protein. Better understanding of the protein network of Philadelphia positive leukemic cells will prove to be helpful in getting a step closer to personalized medicine Daha fazlası Daha az

Farooqi, A.A. | Qureshi, M.Z. | Attar, Rukset | Alhewairini, S.S. | Fayyaz, S. | Sabitaliyevich, U.Y. | Alaaeddine, N.

Review | 2019 | Cellular and molecular biology (Noisy-le-Grand, France)65 ( 6 ) , pp.1 - 5

Central dogma of molecular biology, a term coined by Francis Crick in 1958 was considered to be the cornerstone of molecular biology unless molecular biologists challenged the idea after ground-breaking discovery of non-coding RNAs. Discovery of microRNAs marked a new era and revolutionized our understanding related to puzzling mysteries about intermediate steps between transcription and translation. Technological advancements have spawned a multitude of platforms for profiling of long-noncoding RNAs and miRNAs in different cancers. Detailed investigation of mRNA targets of miRNAs has enabled high-order analyses of interconnected ne . . .tworks and revealed affected pathways in different cancers. miR-143 has emerged as a multi-talented tumor suppressor microRNA having considerable ability to inhibit and prevent cancer via regulation of myriad of oncogenes. In this review, we will summarize most recent evidence related to characteristically unique ability of miR-143 to target different oncogenic mRNAs in different cancers. We will also comprehensively discuss how scientists have identified multiple long non-coding RNAs reportedly involved in promoting the expression of oncogenes by interfering with miR-143 mediated targeting of these oncogenes. Because of excellent ability of miR-143 to effectively target oncogenic mRNAs, researchers have started to focus on use of miR-143 mimics to restore expression of miR-143 in various cancers Daha fazlası Daha az

Jabeen, S. | Qureshi, M.Z. | Attar, Rukset | Aslam, A. | Kanwal, S. | Khalid, S. | Ismail, M.

Review | 2016 | Cellular and Molecular Biology62 ( 7 ) , pp.110 - 117

Data obtained from high-throughput technologies has started to shed light on the interplay between signal transduction cascades and chromatin modifications thus adding another layer of complexity to the already complex regulation of the protein network. Based on the insights gleaned from almost a decade of research, it has now been convincingly revealed that sesquiterpenes effectively modulated different intracellular signaling cascades in different cancers. In this review we summarize how sesquiterpenes mediated Wnt, Shh, Notch and TRAIL induced signaling cascades. © 2016 by the C.M.B. Association. All rights reserved.

Farooqi, A.A. | Jabeen, S. | Attar, Rukset | Yaylim, I. | Xu, B.

Review | 2018 | Journal of Cellular Biochemistry119 ( 12 ) , pp.9664 - 9674

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/ß-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. © 2018 Wiley Periodicals, Inc Daha fazlası Daha az

Lin, X. | Aslam, A. | Attar, Rukset | Yaylim, I. | Qureshi, M.Z. | Hasnain, S. | Farooqi, A.A.

Review | 2016 | Cellular and Molecular Biology62 ( 1 ) , pp.45 - 50

Research over the decades has gradually and sequentially shown that both intratumor heterogeneity and multifocality make prostate cancer difficult to target. Different challenges associated with generation of risk-stratification tools that correlate genomic landscape with clinical outcomes severely influence clinical efficacy of therapeutic strategies. Androgen receptor mediated signaling has gained great appreciation and rewiring of AR induced signaling cascade in absence of androgen, structural variants of AR have provided near complete resolution of genomic landscape and underlying mechanisms of prostate cancer. In this review we . . . have attempted to provide an overview of most recent advancements in our knowledge related to different signaling cascades including TGF, SHH, Notch, JAK-STAT in prostate cancer progression and development. © 2016 by the C.M.B. Association Daha fazlası Daha az

Attar, Rukset | Attar, E.

Review | 2008 | Transfusion and Apheresis Science38 ( 3 ) , pp.245 - 251

Stem cells can be used in different areas of obstetrics and gynecology. Adult stem cells are specialized cells found within many tissues of the body where they function in tissue homeostasis and repair. In vitro they have been shown to differentiate into a wide variety of cell types. Hematopoietic stem cells (HSC) have been used to set up therapeutic strategies for the treatment of gynecological solid tumors such as ovarian cancer. Stem cells can be used for prenatal transplantation and in utero gene therapy. Also stem cells can be used in infertility and IVF for research and treatment. © 2008 Elsevier Ltd. All rights reserved.

Farooqi, A.A. | Attar, Rukset | Bageshlooyafshar, B. | Sabitaliyevich, U.Y. | Nurmurzayevich, S.B. | Yelekenova, A.B. | Gormus, U.

Review | 2019 | Cellular and molecular biology (Noisy-le-Grand, France)65 ( 3 ) , pp.72 - 75

Kisspeptin-driven intracellular signaling has captured enormous attention because of its central role in cancer onset and progression. Wealth of information has helped us to develop a better understanding of the critical roles of Kisspeptin-mediated signaling in different cancers. However, astonishingly, we have not yet drilled down deep into the mysterious aspects associated with non-coding RNA mediated regulation of Kisspeptin-driven signaling. Therefore, in this mini-review, we will comprehensively analyze available evidence related to miRNAs and long non-coding RNAs (LncRNAs) and their ability to modulate Kisspeptin-mediated sig . . .naling. There are visible knowledge gaps about interplay between non-coding RNAs and Kisspeptin-mediated signaling. It will be appropriate to say that we have just started to scratch the surface of an entirely new regulatory layer of Kisspeptin-mediated transduction cascade. Mechanistically, it has been revealed that inhibition of Kisspeptin mediated signaling activated and stimulated the entry of NF?B into the nucleus to stimulate expression of proteins which can sequentially inactivate tumor suppressor miRNAs. miRNAs have also an instrumental role in regulation of proteins which post-translationally modify and inhibit KISS1 expression. It is becoming progressively more understandable that LncRNAs act as miRNA sponges and protect oncogenic mRNAs. However, these facets are also incompletely investigated. Identification of LncRNAs which interfere with Kisspeptin-mediated pathway either through acting as miRNA sponges or working with methylation-associated machinery will be helpful in sharpening the resolution of the pixels of the regulatory network which shapes Kisspeptin-mediated signaling Daha fazlası Daha az

Qureshi, M.Z. | Jabeen, S. | Butt, G. | Aslam, A. | Naqvi, S.K.-U.-H. | Attar, Rukset | Farooqi, A.A.

Review | 2016 | Cellular and Molecular Biology62 ( 5 ) , pp.38 - 43

Smad ubiquitin regulatory factors (SMURFS) belong to the HECT- family of E3 ubiquitin ligases. This family has two members, SMURF1 and SMURF2. SMURFs have emerged as well studied negative regulators of TGF induced intracellular signaling. However, increasingly it is being realized that SMURFs tactfully modulate an array of proteins in different cancers. This review sets spotlight on how SMURF1 and SMURF2 communicate with effectors of different signaling pathways during the multistep progression to cancer. We also summarize how microRNAs (miRNAs) effectively control SMURFs in different cancers. Role of SMURFs is context dependent in . . .different cancers and better concepts related to miRNA regulation of SMURFs in different stages and steps of cancer will be helpful in efficient translation of laboratory findings to clinic. © 2016 by the C.M.B. Association. All rights reserved Daha fazlası Daha az