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  1. Article ; Online: Resveratrol as a Promising Nutraceutical: Implications in Gut Microbiota Modulation, Inflammatory Disorders, and Colorectal Cancer.

    Prakash, Vidhya / Bose, Chinchu / Sunilkumar, Damu / Cherian, Robin Mathew / Thomas, Shwetha Susan / Nair, Bipin G

    International journal of molecular sciences

    2024  Volume 25, Issue 6

    Abstract: Natural products have been a long-standing source for exploring health-beneficial components from time immemorial. Modern science has had a renewed interest in natural-products-based drug discovery. The quest for new potential secondary metabolites or ... ...

    Abstract Natural products have been a long-standing source for exploring health-beneficial components from time immemorial. Modern science has had a renewed interest in natural-products-based drug discovery. The quest for new potential secondary metabolites or exploring enhanced activities for existing molecules remains a pertinent topic for research. Resveratrol belongs to the stilbenoid polyphenols group that encompasses two phenol rings linked by ethylene bonds. Several plant species and foods, including grape skin and seeds, are the primary source of this compound. Resveratrol is known to possess potent anti-inflammatory, antiproliferative, and immunoregulatory properties. Among the notable bioactivities associated with resveratrol, its pivotal role in safeguarding the intestinal barrier is highlighted for its capacity to prevent intestinal inflammation and regulate the gut microbiome. A better understanding of how oxidative stress can be controlled using resveratrol and its capability to protect the intestinal barrier from a gut microbiome perspective can shed more light on associated physiological conditions. Additionally, resveratrol exhibits antitumor activity, proving its potential for cancer treatment and prevention. Moreover, cardioprotective, vasorelaxant, phytoestrogenic, and neuroprotective benefits have also been reported. The pharmaceutical industry continues to encounter difficulties administering resveratrol owing to its inadequate bioavailability and poor solubility, which must be addressed simultaneously. This report summarizes the currently available literature unveiling the pharmacological effects of resveratrol.
    MeSH term(s) Humans ; Resveratrol/pharmacology ; Resveratrol/therapeutic use ; Gastrointestinal Microbiome ; Polyphenols/pharmacology ; Dietary Supplements ; Colorectal Neoplasms/drug therapy
    Chemical Substances Resveratrol (Q369O8926L) ; Polyphenols
    Language English
    Publishing date 2024-03-16
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2019364-6
    ISSN 1422-0067 ; 1422-0067 ; 1661-6596
    ISSN (online) 1422-0067
    ISSN 1422-0067 ; 1661-6596
    DOI 10.3390/ijms25063370
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Systematic understanding of anti-tumor mechanisms of Tamarixetin through network and experimental analyses.

    Shaji, Sanu K / Drishya, G / Sunilkumar, Damu / Suravajhala, Prashanth / Kumar, Geetha B / Nair, Bipin G

    Scientific reports

    2022  Volume 12, Issue 1, Page(s) 3966

    Abstract: Tamarixetin, a flavonoid derived from Quercetin, was shown to possess anti-cancer properties in various types of cancer. However, the mechanism of action of this compound is not well understood. Observations from reverse docking and network pharmacology ... ...

    Abstract Tamarixetin, a flavonoid derived from Quercetin, was shown to possess anti-cancer properties in various types of cancer. However, the mechanism of action of this compound is not well understood. Observations from reverse docking and network pharmacology analysis, were validated by cell based studies to analyse the chemotherapeutic potential and elucidate the molecular mechanism of action of Tamarixetin in breast cancer. In silico analysis using reverse docking and PPI analysis clearly indicated that out of 35 proteins targeted by Tamarixetin, the top 3 hub genes, namely, AKT1, ESR1 and HSP90AA1, were upregulated in breast tumor tissues and more importantly showed strong negative correlation to breast cancer patient survival. Furthermore, the KEGG pathway analysis showed enrichment of target proteins of Tamarixetin in 33 pathways which are mainly involved in neoplastic signalling. In vitro cell-based studies demonstrated that Tamarixetin could inhibit cell proliferation, induce ROS and reduce mitochondrial membrane potential, leading to cell death. Tamarixetin induced cell cycle arrest at G2/M phase and inhibited the migration as well as the invasion of breast cancer cells. Taken together, the combination of in silico and in vitro approaches used in the present study clearly provides evidence for the chemotherapeutic potential of Tamarixetin in breast cancer.
    MeSH term(s) Breast Neoplasms/drug therapy ; Disaccharides/pharmacology ; Drugs, Chinese Herbal/pharmacology ; Female ; Humans ; Molecular Docking Simulation ; Quercetin/analogs & derivatives ; Quercetin/pharmacology ; Quercetin/therapeutic use
    Chemical Substances Disaccharides ; Drugs, Chinese Herbal ; tamarixetin (73WRA8Z8M8) ; Quercetin (9IKM0I5T1E)
    Language English
    Publishing date 2022-03-10
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/s41598-022-07087-6
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Nuclear factor-κB plays an important role in Tamarixetin-mediated inhibition of matrix metalloproteinase-9 expression.

    Shaji, Sanu K / G, Drishya / Sunilkumar, Damu / Pandurangan, Nanjan / Kumar, Geetha B / Nair, Bipin G

    European journal of pharmacology

    2020  Volume 893, Page(s) 173808

    Abstract: Flavonoids possess a broad spectrum of pharmacological properties, including anti-cancer, anti-oxidant and immunomodulatory activities. The current study explored the potential of some less-studied flavonoids in inhibiting Matrix Metalloproteinase-9 (MMP- ...

    Abstract Flavonoids possess a broad spectrum of pharmacological properties, including anti-cancer, anti-oxidant and immunomodulatory activities. The current study explored the potential of some less-studied flavonoids in inhibiting Matrix Metalloproteinase-9 (MMP-9), a prominent biomarker, upregulated in a variety of cancers and known to promote migration and invasion of cancer cells. Amongst these, Tamarixetin, a naturally occurring flavonoid derivative of Quercetin, demonstrated significant dose-dependent inhibition of MMP-9 expression. Furthermore, a substantial inhibition of migration, invasion and clonogenic potential of HT1080 cells was also observed in the presence of Tamarixetin, which further suggests its role as a potential anti-cancer agent. It is noteworthy that Tamarixetin inhibits nuclear translocation as well the activity of nuclear factor kappa B (NFκB), both of which are functions essential for the activation of MMP-9 in promoting tumorigenesis. Additionally, the endogenous regulators of MMP-9 that tightly control its activity were also modulated by Tamarixetin, as evident from the 1.9 fold increase in the expression of Tissue Inhibitor of Metalloproteinase-1 (TIMP-1), with a concomitant 2.2 fold decrease in Matrix Metalloproteinase-14 (MMP-14) expression. The results obtained were further corroborated in three dimensional (3D) tumor models, which showed significant inhibition of MMP-9 activity as well as reduced invasive potential in the presence of Tamarixetin. Taken together, our observations demonstrate for the first time, the anti-invasive potential of Tamarixetin in cancer cells, indicating its possible use as a template for novel therapeutic applications.
    MeSH term(s) A549 Cells ; Active Transport, Cell Nucleus ; Antineoplastic Agents, Phytogenic/pharmacology ; Cell Movement/drug effects ; Cell Proliferation/drug effects ; Disaccharides/pharmacology ; Down-Regulation ; Fibrosarcoma/drug therapy ; Fibrosarcoma/enzymology ; Fibrosarcoma/genetics ; Fibrosarcoma/pathology ; Gene Expression Regulation, Neoplastic ; Humans ; Matrix Metalloproteinase 9/genetics ; Matrix Metalloproteinase 9/metabolism ; Matrix Metalloproteinase Inhibitors/pharmacology ; NF-kappa B/genetics ; NF-kappa B/metabolism ; Neoplasm Invasiveness ; Quercetin/analogs & derivatives ; Quercetin/pharmacology ; Signal Transduction ; Spheroids, Cellular
    Chemical Substances Antineoplastic Agents, Phytogenic ; Disaccharides ; Matrix Metalloproteinase Inhibitors ; NF-kappa B ; tamarixetin (73WRA8Z8M8) ; Quercetin (9IKM0I5T1E) ; MMP9 protein, human (EC 3.4.24.35) ; Matrix Metalloproteinase 9 (EC 3.4.24.35)
    Language English
    Publishing date 2020-12-17
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 80121-5
    ISSN 1879-0712 ; 0014-2999
    ISSN (online) 1879-0712
    ISSN 0014-2999
    DOI 10.1016/j.ejphar.2020.173808
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 522: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (1.OG)
    ab Jg. 2022: Lesesaal (EG)

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  4. Article: Analysis of microarray data for identification of key microRNA signatures in glioblastoma multiforme.

    Shaji, Sanu K / Sunilkumar, Damu / Mahalakshmi, N V / Kumar, Geetha B / Nair, Bipin G

    Oncology letters

    2019  Volume 18, Issue 2, Page(s) 1938–1948

    Abstract: Glioblastoma multiforme (GBM) is one of the most malignant types of glioma known for its reduced survival rate and rapid relapse. Previous studies have shown that the expression patterns of different microRNAs (miRNA/miR) play a crucial role in the ... ...

    Abstract Glioblastoma multiforme (GBM) is one of the most malignant types of glioma known for its reduced survival rate and rapid relapse. Previous studies have shown that the expression patterns of different microRNAs (miRNA/miR) play a crucial role in the development and progression of GBM. In order to identify potential miRNA signatures of GBM for prognostic and therapeutic purposes, we downloaded and analyzed two expression data sets from Gene Expression Omnibus profiling miRNA patterns of GBM compared with normal brain tissues. Validated targets of the deregulated miRNAs were identified using MirTarBase, and were mapped to Search Tool for the Retrieval of Interacting Genes/Proteins, Database for Annotation, Visualization and Integrated Discovery and Kyoto Encyclopedia of Genes and Genomes databases in order to construct interaction networks and identify enriched pathways of target genes. A total of 6 miRNAs were found to be deregulated in both expression datasets studied. Pathway analysis demonstrated that most of the target genes were enriched in signaling cascades connected to cancer development, such as 'Pathways in cancer', 'Focal adhesion' and 'PI3K-Akt signaling pathway'. Of the five target genes that were enriched in the glioblastoma pathway, in the WikiPathway database, both HRas proto-oncogene, GTPase and MET proto-oncogene, receptor tyrosine kinase target genes of hsa-miR-139-5p, were found to be significantly associated with patient survival. The present study may thus form the basis for further exploration of hsa-miR-139-5p, not only as a therapeutic agent, but also as a diagnostic biomarker for GBM as well as a predictive marker for patient survival.
    Language English
    Publishing date 2019-06-24
    Publishing country Greece
    Document type Journal Article
    ZDB-ID 2573196-8
    ISSN 1792-1082 ; 1792-1074
    ISSN (online) 1792-1082
    ISSN 1792-1074
    DOI 10.3892/ol.2019.10521
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Oxyresveratrol drives caspase-independent apoptosis-like cell death in MDA-MB-231 breast cancer cells through the induction of ROS.

    Sunilkumar, Damu / Drishya, G / Chandrasekharan, Aneesh / Shaji, Sanu K / Bose, Chinchu / Jossart, Jennifer / Perry, J Jefferson P / Mishra, Nandita / Kumar, Geetha B / Nair, Bipin G

    Biochemical pharmacology

    2019  Volume 173, Page(s) 113724

    Abstract: Earlier studies from our laboratory have demonstrated that Oxyresveratrol (OXY), a hydroxyl-substituted stilbene, exhibits potent inhibition of human melanoma cell proliferation. The present study defines a cytotoxic effect of OXY on the highly chemo- ... ...

    Abstract Earlier studies from our laboratory have demonstrated that Oxyresveratrol (OXY), a hydroxyl-substituted stilbene, exhibits potent inhibition of human melanoma cell proliferation. The present study defines a cytotoxic effect of OXY on the highly chemo-resistant, triple-negative human breast cancer cell line MDA-MB-231. OXY-mediated cell death resulted in accumulation of cells at the sub-G1 phase of the cell cycle, induced chromatin condensation, DNA fragmentation, phosphatidylserine externalization and PARP cleavage, indicative of apoptosis. Interestingly, morphology and cell viability studies with the pan-caspase inhibitor, QVD-OPH revealed that OXY-induced cell death was caspase-independent. Docking studies also showed that OXY can bind to the S1 site of caspase-3, and could also exert an inhibitory effect on this executioner caspase. The immunoblot analysis demonstrating the absence of caspase cleavage during cell death further confirmed these findings. OXY was also observed to induce the production of reactive oxygen species, which caused the depolarization of the mitochondrial membrane resulting in translocation of Apoptosis Inducing Factor (AIF) into the nucleus. Pretreatment of the cells with N-Acetyl Cysteine antioxidant prevented cell death resulting from OXY treatment. Thus, OXY initiates ROS-mediated, apoptosis-like cell death, involving mitochondrial membrane depolarization, translocation of AIF into the nucleus, and DNA fragmentation, resulting in caspase-independent cell death in MDA-MB-231 cells. The cytotoxicity manifested by OXY was also observed in 3D cell culture models and primary cells, thereby providing a basis for the utilization of OXY as a novel template for the future design of anticancer therapeutics.
    MeSH term(s) Antineoplastic Agents/chemistry ; Antineoplastic Agents/metabolism ; Antineoplastic Agents/pharmacology ; Apoptosis/drug effects ; Breast Neoplasms/metabolism ; Breast Neoplasms/pathology ; Caspase 3/chemistry ; Caspase 3/metabolism ; Caspases/chemistry ; Caspases/metabolism ; Cell Line, Tumor ; Cell Survival/drug effects ; Female ; Humans ; Membrane Potential, Mitochondrial/drug effects ; Mitochondria/drug effects ; Mitochondria/metabolism ; Molecular Docking Simulation ; Plant Extracts/chemistry ; Plant Extracts/metabolism ; Plant Extracts/pharmacology ; Protein Binding ; Reactive Oxygen Species/metabolism ; Stilbenes/chemistry ; Stilbenes/metabolism ; Stilbenes/pharmacology
    Chemical Substances Antineoplastic Agents ; Plant Extracts ; Reactive Oxygen Species ; Stilbenes ; puag-haad (4721-07-7) ; Caspase 3 (EC 3.4.22.-) ; Caspases (EC 3.4.22.-)
    Language English
    Publishing date 2019-11-20
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 208787-x
    ISSN 1873-2968 ; 0006-2952
    ISSN (online) 1873-2968
    ISSN 0006-2952
    DOI 10.1016/j.bcp.2019.113724
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 19: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (1.OG)
    ab Jg. 2022: Lesesaal (EG)

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  6. Article ; Online: Discovery of lesser known flavones as inhibitors of NF-κB signaling in MDA-MB-231 breast cancer cells--A SAR study.

    Amrutha, K / Nanjan, Pandurangan / Shaji, Sanu K / Sunilkumar, Damu / Subhalakshmi, K / Rajakrishna, Lakshmi / Banerji, Asoke

    Bioorganic & medicinal chemistry letters

    2014  Volume 24, Issue 19, Page(s) 4735–4742

    Abstract: Seventeen flavonoids with different substitutions were evaluated for inhibition of nuclear factor-κB (NF-κB) signaling in the invasive breast cancer cell line MDA-MB-231. They were screened using an engineered MDA-MB-231 cell line reporting NF-κB ... ...

    Abstract Seventeen flavonoids with different substitutions were evaluated for inhibition of nuclear factor-κB (NF-κB) signaling in the invasive breast cancer cell line MDA-MB-231. They were screened using an engineered MDA-MB-231 cell line reporting NF-κB activation. The modulation of expression of two NF-κB regulated genes involved in tumorigenesis, matrix metalloproteinase-9 (MMP-9), and cyclooxygenase-2 (COX-2) were also analyzed in these cells. Among the compounds tested, all except gossypetin and quercetagetin inhibited the activation of NF-κB, and the expression of MMP-9 and COX-2 to different degree. Methylated flavone, chrysoeriol (luteolin-3'-methylether), was found to be the most potent inhibitor of MMP-9 and COX-2 expressions. The effect of chrysoeriol on cell proliferation, cell cycle, apoptosis and metastasis was analyzed by established methods. Chrysoeriol caused cell cycle arrest at G2/M and inhibited migration and invasion of MDA-MB-231 cells. The structure-activity relations amongst the flavonoids as NF-κB signaling inhibitors was studied. The study indicates differences between the actions of various flavonoids on NF-κB activation and on the biological activities of breast cancer cells. Flavones in general, were more active than the corresponding flavonols.
    MeSH term(s) Apoptosis/drug effects ; Cell Cycle/drug effects ; Cell Line, Tumor ; Cell Movement/drug effects ; Dose-Response Relationship, Drug ; Drug Discovery ; Flavones/chemical synthesis ; Flavones/chemistry ; Flavones/pharmacology ; Humans ; Molecular Structure ; NF-kappa B/antagonists & inhibitors ; NF-kappa B/metabolism ; Signal Transduction/drug effects ; Structure-Activity Relationship
    Chemical Substances Flavones ; NF-kappa B
    Language English
    Publishing date 2014-10-01
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1063195-1
    ISSN 1464-3405 ; 0960-894X
    ISSN (online) 1464-3405
    ISSN 0960-894X
    DOI 10.1016/j.bmcl.2014.07.093
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Zs.A 3203: Show issues Location:
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