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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

Development and characterization of liposomal formulations for rapamycin delivery and investigation of their antiproliferative effect on MCF7 cells

Rouf, M.A. | Vural, I. | Renoir, J.M. | Hincal, A.A.

Article | 2009 | Journal of Liposome Research19 ( 4 ) , pp.322 - 331

Rapamycin (Sirolimus) is a macrolide lactone with antifungal, immunosuppressant, and antiproliferative actions. The mechanism of rapamycin action involves the inhibition of mTOR and subsequent cytostasis. Rapamycin also prevents angiogenesis in tumors and can prevent cancer cells' resistance to other chemotherapeutic agents. However, very poor water solubility, bioavailability, only slight solubility in acceptable parenteral excipients, chemical instability, and major sequestration (95%) of free rapamycin into the erythrocytes have prevented its development as an anticancer drug. To address these problems, it was attempted to develo . . .p liposomal rapamycin delivery systems in this study. Conventional and pegylated liposomes were prepared with various lipid and cholesterol ratios. They were then characterized; these liposomes contained 0.680.90mg of rapamycin per milliliter of liposome suspension. Having suitable particle size, these liposomes successfully retained the entrapped drug. Both types of liposomes were found to be effective; however, conventional liposomes showed better antiproliferative activity against MCF-7 cells than pegylated liposomes. But, pegylated liposome showed better stability than conventional liposomes. In conclusion, the enhanced permeability and retention effercts of tumors should provide the opportunity for pegylated liposomal rapamycin to be applied as an intravenous drug-delivery system for targeted delivery to cancer cells, avoiding the major sequestration of free rapamycin into the erythrocytes Daha fazlası Daha az

Hydrogen peroxide prolongs mitotic arrest in a dose dependent manner and independently of the spindle assembly checkpoint activity in saccharomyces cerevisiae

Atalay, P.B. | Asci, O. | Kaya, F.O. | Tuna, B.G.

Article | 2017 | Acta Biologica Hungarica68 ( 4 ) , pp.477 - 489

Oxidative stress and chromosome missegregation are important factors that are linked to aneuploidy. A major reason for chromosome missegragation is the inappropriate activity of the spindle assembly checkpoint (SAC), a conserved surveillance mechanism that monitors the state of kinetochore-microtubule attachments to ensure equal chromosome segregation in mitosis. SAC-activation induces a prolonged mitotic arrest. Mitosis is considered the most vulnerable cell cycle phase to several external signals, therefore increasing the time cells spent in this phase via mitotic arrest induction by SAC-activating agents is favorable for cancer t . . .herapy. Cancer cells also display elevated oxidative stress due to abnormally high production of reactive oxygen species (ROS). However, the effect of increased oxidative stress on the duration of mitotic arrest remains largely unknown. In this study, we investigated the effect of H 2 O 2 -induced oxidative stress on the mitotic arrest induced by a SAC-activating agent (nocodazole) in Saccharomyces cerevisiae. Our data suggest that oxidative stress prolongs SAC-activation induced mitotic arrest in a dose dependent manner. We, in addition, investigated the effect of H 2 O 2 treatment on the mitotic arrest induced independently of SAC-activation by using a conditional mutant (cdc23) and showed that the effect of H 2 O 2 -induced oxidative stress on mitotic arrest is independent of the SAC activity. © 2017 Akademiai Kiado Rt. All rights reserved 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

Reliability and Validity of Turkish Version of the Caregiver Quality of Life Index Cancer Scale

Yakar, H.K. | Pinar, R.

Article | 2013 | Asian Pacific Journal of Cancer Prevention14 ( 7 ) , pp.4415 - 4419

Background: Measuring effects of cancer on family caregivers is important to develop methods which can improve their quality of life (QOL). Nevertheless, up to now, only a few tools have been developed to be used in this group. Among those, the Caregiver Quality of Life Index-Cancer Scale (CQOLC) has met minimum psychometric criteria in different populations in spite of conflicting results. The present study was conducted to evaluate reliability and validity of CQOLC among Turkish cancer family caregivers. Materials and Methods: The CQOLC was administered to 120 caregivers, along with Beck Depression Inventory (BDI), Medical Outcome . . .s Study MOS 36- Item Short Form Health Survey (SF-36), State-Trait Anxiety Inventory (STAI), and Multidimensional Scale of Perceived Social Support (MSPSS). Internal consistency and test-retest stability were used to investigate reliability. Construct validity was examined by using known group method, convergent, and divergent validity. For the known group method, we hypothesized that CQOLC scores would differ between depressed and non-depressed subjects. We investigated convergent validity by correlating scores for CQOLC with scores for other similar measures including SF-36 and STAI. The MSPSS was completed at the same time as CQOLC to provide divergent validity. Results: The values for internal consistency and test-retest correlation were 0.88 and 0.96, respectively. The CQOLC discriminated those who were depressed from those who were not. Convergent validity supported strong correlations between CQOLC scores and two main component scores (PCS, MCS) in SF-36 although there was a weak correlation between CQOLC and STAI scores. Regarding divergent validity, the correlation between CQOLC and MSPSS was in the low range, as expected. Conclusions: The Turkish CQOLC is a reliable and valid tool and it can be utilized to determine QOL of family caregivers 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

Safety, feasibility, and efficacy of capecitabine maintenance in patients with advanced gastric cancer: A retrospective study

Eren, O.O. | Ozturk, M.A. | Sonmez, O.U. | Oyan, B.

Article | 2016 | American Journal of Therapeutics23 ( 6 ) , pp.1 - 6

Gastric cancer is still one of the cancers with highest mortality. Most patients present with advancedstage disease. Palliative chemotherapy is usually the only treatment option for patients with advanced gastric cancer (AGC). Maintenance chemotherapy is an evolving concept in medical oncology. Maintenance chemotherapy can be administered with the same drug(s) in the initial regimen or with an alternative agent. In this article, we report our experience with capecitabine as a maintenance agent for patients with AGC. No treatment-related death was observed due to use of capecitabine. Median progression-free survival was 10.4 months, . . .and median overall survival was 19.7 months. Activity and toxicity profile of capecitabine seems favorable as a maintenance agent in AGC. We believe that capecitabine deserves further trials as a maintenance agent for patients with AGC. Copyright © 2015 Wolters Kluwer Health, Inc 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.1 - 6

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

Cancer cell Cytotoxicities of 1-(4-substitutedbenzoyl)-4-(4-chlorobenzhydryl)piperazine derivatives

Yarim, M. | Koksal, M. | Durmaz, I. | Atalay, R.

Article | 2012 | International Journal of Molecular Sciences13 ( 7 ) , pp.8071 - 8085

A series of novel 1-(4-substitutedbenzoyl)-4-(4-chlorobenzhydryl)piperazine derivatives 5a-g was designed by a nucleophilic substitution reaction of 1-(4-chlorobenzhydryl)piperazine with various benzoyl chlorides and characterized by elemental analyses, IR and 1H nuclear magnetic resonance spectra. Cytotoxicity of the compounds was demonstrated on cancer cell lines from liver (HUH7, FOCUS, MAHLAVU, HEPG2, HEP3B), breast (MCF7, BT20, T47D, CAMA-1), colon (HCT-116), gastric (KATO-3) and endometrial (MFE-296) cancer cell lines. Time-dependent cytotoxicity analysis of compound 5a indicated the long-term in situ stability of this compoun . . .d. All compounds showed significant cell growth inhibitory activity on the selected cancer cell lines. © 2012 by the authors; licensee MDPI, Basel, Switzerland 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

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