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Citrus fruits and their bioactive ingredients: Leading four horsemen from front

Farooqi, A.A. | Wang, Z. | Hasnain, S. | Attar, Rukset | Aslam, A. | Mansoor, Q. | Ismail, M.

Note | 2015 | Asian Pacific Journal of Cancer Prevention16 ( 6 ) , pp.2575 - 2580

Cancer is a multifaceted and genomically complex disease and rapidly accumulating high impact research is deepening our understanding related to the mechanisms underlying cancer development, progression and resistance to therapeutics. Increasingly it is being realized that genetic/epigenetic mutations, inactivation of tumor suppressor genes, overexpression of oncogenes, deregulation of intracellular signaling cascades and loss of apoptosis are some of the extensively studied aspects. Confluence of information suggested that rapidly developing resistance to therapeutics is adding another layer of complexity and overwhelmingly increas . . .ing preclinical studies are identifying different natural agents with efficacy and minimal off-target effects. We partition this multi-component review into citrus fruits and their bioactive ingredients mediating rebalancing of pro- and anti-apoptotic proteins to induce apoptosis in resistant cancer cells. We also discuss how oncogenic protein networks are targeted in cancer cells and how these findings may be verified in preclinical studies Daha fazlası Daha az

Regulation of signal transduction cascades by Pterostilbenes in different cancers: Is it a death knell for oncogenic pathways

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

Interplay of long non-coding RNAs and TGF/SMAD signaling in different cancers

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

Article | 2018 | Cellular and Molecular Biology64 ( 15 ) , pp.1 - 6

Based on the exciting insights gleaned from decades of ground-breaking research, it has become evident that deregulated signaling pathways play instrumental role in cancer development and progression. Interestingly discovery of non-coding RNAs has revolutionized our understanding related to transcription, post-transcription and translation. Modern era has witnessed landmark discoveries in the field of molecular cancer and non-coding RNA biology has undergone tremendous broadening. There has been an exponential growth in the list of publications related to non-coding RNAs and overwhelmingly increasing classes of non-coding RNAs are a . . .dding new layers of complexity to already complicated nature of cancer. Regulation of TGF/SMAD signaling by miRNAs and LncRNAs has opened new horizons for therapeutic targeting of TGF/SMAD pathway. In this review we have set spotlight on central role of LncRNAs in modulation of TGF/ SMAD pathway. Major proportion of the available evidence is underlining positive role of LncRNAs in contextual regulation of TGF/SMAD pathway. LncRNAs are vital to these regulatory networks because they provide a background support to make the TGF/SMAD mediated intracellular signaling more smooth or make transduction cascade more flexible in response to cues from extracellular environment. Therefore, in accordance with this notion, MALAT1, OIP5-AS1, MIR100HG, HOTAIR, ANRIL, PVT1, AFAP1-AS1, SPRY4-IT, ZEB2NAT, TUG1 and Lnc-SNHG1 have been reported to positively regulate TGF/SMAD signaling. In this review, we have focused on the regulation of TGF/SMAD signaling by LncRNAs and how these non-coding RNAs can be therapeutically exploited. Short-interfering RNA (siRNA) and natural products are currently being tested for efficacy against different LncRNAs. Nanotechnological strategies to efficiently deliver LncRNA-targeting siRNAs are also currently being investigated in different cancers. © 2018 by the C.M.B. Association. All rights reserved Daha fazlası Daha az

TRAIL and Bortezomib: Killing cancer with two stones

Qureshi, M.Z. | Romero, M.A. | Attar, Rukset | Javed, Z. | Farooqi, A.A.

Article | 2015 | Asian Pacific Journal of Cancer Prevention16 ( 4 ) , pp.1671 - 1674

Cancer genomics and proteomics have undergone considerable broadening in the past decades and increasingly it is being realized that solid/liquid phase microarrays and high-throughput resequencing have provided platforms to improve our existing knowledge of determinants of cancer development, progression and survival. Loss of apoptosis is a widely and deeply studied process and different approaches are being used to restore apoptosis in resistant cancer phenotype. Modulating the balance between pro-apoptotic and anti-apoptotic proteins is essential to induce apoptosis. It is becoming more understood that pharmacological inhibition o . . .f the proteasome might prove to be an effective option in improving TRAIL induced apoptosis in cancer cells. Keeping in view rapidly accumulating evidence of carcinogenesis, metastasis, resistance against wide ranging therapeutics and loss of apoptosis, better knowledge regarding tumor suppressors, oncogenes, pro-apoptotic and anti-apotptic proteins will be helpful in translating the findings from benchtop to bedside Daha fazlası Daha az

Targeting of BCR-ABL: Lessons learned from BCR-ABL inhibition

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

Natural products are the future of anticancer therapy: Preclinical and clinical advancements of viscum album phytometabolites

Attar, Rukset | Tabassum, S. | Fayyaz, S. | Ahmad, M.S. | Nogueira, D.R. | Yaylim, I. | Ismail, M.

Article | 2015 | Cellular and Molecular Biology61 ( 6 ) , pp.62 - 68

Cancer is a multifaceted and genomically complex disease. Research over the years has gradually provided a near complete resolution of cancer landscape and it is now known that genetic/epigenetic mutations, inactivation of tumor suppressors, Overexpression of oncogenes, spatio-temporally dysregulated intracellular signaling cascades, epithelial to mesenchymal transition (EMT), metastasis and loss of apoptosis are some of the most extensively studied biological mechanisms that underpin cancer development and progression. Increasingly it is being realized that current therapeutic interventions are becoming ineffective because of tumor . . . heterogeneity and rapidly developing resistance against drugs. Considerable biological activities exerted by bioactive ingredients isolated from natural sources have revolutionized the field of natural product chemistry and rapid developments in preclinical studies are encouraging. Viscum album has emerged as a deeply studied natural source with substantial and multifaceted biological activities. In this review we have attempted to provide recent breakthroughs in existing scientific literature with emphasis on targeting of protein network in cancer cells. We partition this review into different sections, highlighting latest information from cell culture studies, preclinical and clinically oriented studies. We summarized how bioactive ingredients of Viscum album modulated extrinsic and intrinsic pathways in cancer cells. However, surprisingly, none of the study reported stimulatory effects on TRAIL receptors. The review provided in-depth analysis of how Viscum album modulated Endoplasmic Reticulum Stress in cancer cells and how bioactive chemicals tactfully targeted cytoskeletal machinery in cancer cells as evidenced by cell culture studies. It is noteworthy that Viscum album has entered into various phases of clinical trials, however, there are still knowledge gaps in our understanding regarding how various bioactive constituents of Viscum album modulate intracellular signaling cascades in cancer. Better and deeper comprehension oncogenic signaling cascades will prove to be helful in getting a step closer to individualized medicine. © 2015 Daha fazlası Daha az

Maslinic acid as an effective anticancer agent

Lin, X. | Ozbey, U. | Sabitaliyevich, U.Y. | Attar, Rukset | Ozcelik, B. | Zhang, Y. | Farooqi, A.A.

Article | 2018 | Cellular and Molecular Biology64 ( 10 ) , pp.87 - 91

Maslinic acid (2?,3ß-dihydroxyolean-12-en-28-oic acid) is a naturally occurring pentacyclic triterpenic compound. Maslinic acid is gradually gaining attention as an excellent pharmacologically active product because of its premium biological properties. In this review we will focus on chemopreventive properties of Maslinic acid against different cancers. Seemingly, available data is limited and we have yet to unravel how Maslinic acid therapeutically targeted oncogenic cell signal transduction cascades in different cancers. Moreover, there are visible knowledge gaps about the ability of Maslinic acid to modulate oncogenic and tumor . . .suppressor microRNAs in various cancers. © 2018 by the C.M.B. Association Daha fazlası Daha az

NEDD4 Family of E3 Ubiquitin Ligases in Breast Cancer: Spotlight on SMURFs, WWPs and NEDD4

Butt, G. | Yaylim, I. | Attar, Rukset | Aras, A. | Romero, M.A. | Qureshi, M.Z. | Farooqi, A.A.

Book Part | 2019 | Advances in Experimental Medicine and Biology1152 , pp.365 - 375

Massively parallel sequencing, genomic and proteomic technologies have provided near complete resolution of signaling landscape of breast cancer (BCa). NEDD4 family of E3-ubiquitin ligases comprises a large family of proteins particularly, SMURFs (SMURF1, SMURF2), WWPs and NEDD4 which are ideal candidates for targeted therapy. However, it is becoming progressively more understandable that SMURFs and NEDD4 have “split-personalities”. These molecules behave dualistically in breast cancer and future studies must converge on detailed identification of context specific role of these proteins in BCa. Finally, we provide scattered clues of . . . regulation of SMURF2 by oncogenic miRNAs, specifically considering longstanding questions related to regulation of SMURF1 and WWPs by miRNAs in BCa. SMURFS, WWPs and NEDD4 are versatile regulators and represent a fast-growing field in cancer research and better understanding of the underlying mechanisms will be helpful in transition of our knowledge from a segmented view to a more conceptual continuum. © 2019, Springer Nature Switzerland AG Daha fazlası Daha az

MicroRNA-143 as a new weapon against cancer: overview of the mechanistic insights and long non-coding RNA mediated regulation of miRNA-143 in different cancers

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

How sesquiterpenes modulate signaling cascades in cancers

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.

Tudor tells about new twists in the story tale of SMURFs

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

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