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Natural product mediated regulation of death receptors and intracellular machinery: Fresh from the pipeline about TRAIL-mediated signaling and natural TRAIL sensitizers

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

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

Recent updates on true potential of an anesthetic agent as a regulator of cell signaling pathways and non-coding RNAs in different cancers: Focusing on the brighter side of propofol

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

Piperlongumine as anticancer agent: The story so far about killing many birds with one stone

Farooqi, A.A. | Attar, Rukset | Yaylim, I. | Qureshi, M.Z. | Todorovska, M. | Karatoprak, G.S. | Lin, X.

Article | 2018 | Cellular and Molecular Biology64 ( 11 ) , pp.102 - 107

Piperlongumine is a biologically and pharmacologically active constituent of the plant Piper longum. This compound is gradually gaining attention because of its ability to inhibit/prevent different cancers. Modern era of molecular oncology is incomplete without ground-breaking discoveries made in the field of cell signaling pathways. High-throughput technologies have considerably improved our understanding about wide ranging signal transduction cascades which play crucial role in cancer development and progression. It is exciting to note that piperlongumine has been shown to pleiotropically modulate different oncogenic signaling pat . . .hways. We partition this multi-component review into discrete sections and categorically summarize key findings related to excellent ability of piperlongumine to therapeutically target JAK-STAT, NF-kB and PI3K/AKT/mTOR pathways. We also set spotlight on regulation of TRAIL pathway and autophagy by piperlongumine in different cancers. On the basis of the current understanding of piperlongumine, molecular biologists and pharmacologists will develop the next generation of translational studies, which will prove to be helpful in improving the clinical outcome and getting a step closer to personalized medicine. © 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

A novel thiazolidine compound induces caspase-9 dependent apoptosis in cancer cells

Onen-Bayram, F.E. | Durmaz, I. | Scherman, D. | Herscovici, J. | Cetin-Atalay, R.

Article | 2012 | Bioorganic and Medicinal Chemistry20 ( 17 ) , pp.5094 - 5102

The forward chemogenomics strategy allowed us to identify a potent cytotoxic thiazolidine compound as an apoptosis-inducing agent. Chemical structures were designed around a thiazolidine ring, a structure already noted for its anticancer properties. Initially, we evaluated these novel compounds on liver, breast, colon and endometrial cancer cell lines. The compound 3 (ALC67) showed the strongest cytotoxic activity (IC50 ~5 µM). Cell cycle analysis with ALC67 on liver cells revealed SubG1/G1 arrest bearing apoptosis. Furthermore we demonstrated that cytotoxicity of this compound was due to the activation of caspase-9 involved apoptot . . .ic pathway, which is death receptor independent. © 2012 Elsevier Ltd. All rights reserved 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.

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