School Of Basic And Applied Sciences

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    Molecular mechanisms of action of epigallocatechin gallate in cancer: Recent trends and advancement
    (Academic Press, 2020-05-24T00:00:00) Aggarwal, Vaishali; Tuli, Hardeep Singh; Tania, Mousumi; Srivastava, Saumya; Ritzer, Erin E.; Pandey, Anjana; Aggarwal, Diwakar; Barwal, Tushar Singh; Jain, Aklank; Kaur, Ginpreet; Sak, Katrin; Varol, Mehmet; Bishayee, Anupam
    Epigallocatechin gallate (EGCG), also known as epigallocatechin-3-gallate, is an ester of epigallocatechin and gallic acid. EGCG, abundantly found in tea, is a polyphenolic flavonoid that has the potential to affect human health and disease. EGCG interacts with various recognized cellular targets and inhibits cancer cell proliferation by inducing apoptosis and cell cycle arrest. In addition, scientific evidence has illustrated the promising role of EGCG in inhibiting tumor cell metastasis and angiogenesis. It has also been found that EGCG may reverse drug resistance of cancer cells and could be a promising candidate for synergism studies. The prospective importance of EGCG in cancer treatment is owed to its natural origin, safety, and low cost which presents it as an attractive target for further development of novel cancer therapeutics. A major challenge with EGCG is its low bioavailability which is being targeted for improvement by encapsulating EGCG in nano-sized vehicles for further delivery. However, there are major limitations of the studies on EGCG, including study design, experimental bias, and inconsistent results and reproducibility among different study cohorts. Additionally, it is important to identify specific EGCG pharmacological targets in the tumor-specific signaling pathways for development of novel combined therapeutic treatments with EGCG. The present review highlights the ongoing development to identify cellular and molecular targets of EGCG in cancer. Furthermore, the role of nanotechnology-mediated EGCG combinations and delivery systems will also be discussed. � 2020 Elsevier Ltd
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    Molecular mechanisms of action of epigallocatechin gallate in cancer: Recent trends and advancement
    (Academic Press, 2020) Aggarwal, V; Tuli, H.S; Tania, M; Srivastava, S; Ritzer, E.E; Pandey, A; Aggarwal, D; Barwal, T.S; Jain, A; Kaur, G; Sak, K; Varol, M; Bishayee, A.
    Epigallocatechin gallate (EGCG), also known as epigallocatechin-3-gallate, is an ester of epigallocatechin and gallic acid. EGCG, abundantly found in tea, is a polyphenolic flavonoid that has the potential to affect human health and disease. EGCG interacts with various recognized cellular targets and inhibits cancer cell proliferation by inducing apoptosis and cell cycle arrest. In addition, scientific evidence has illustrated the promising role of EGCG in inhibiting tumor cell metastasis and angiogenesis. It has also been found that EGCG may reverse drug resistance of cancer cells and could be a promising candidate for synergism studies. The prospective importance of EGCG in cancer treatment is owed to its natural origin, safety, and low cost which presents it as an attractive target for further development of novel cancer therapeutics. A major challenge with EGCG is its low bioavailability which is being targeted for improvement by encapsulating EGCG in nano-sized vehicles for further delivery. However, there are major limitations of the studies on EGCG, including study design, experimental bias, and inconsistent results and reproducibility among different study cohorts. Additionally, it is important to identify specific EGCG pharmacological targets in the tumor-specific signaling pathways for development of novel combined therapeutic treatments with EGCG. The present review highlights the ongoing development to identify cellular and molecular targets of EGCG in cancer. Furthermore, the role of nanotechnology-mediated EGCG combinations and delivery systems will also be discussed. � 2020 Elsevier Ltd
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    Molecular mechanisms of action of genistein in cancer: Recent advances
    (Frontiers Media S.A., 2019) Tuli H.S.; Tuorkey M.J.; Thakral F.; Sak K.; Kumar M.; Sharma A.K.; Sharma U.; Jain A.; Aggarwal V.; Bishayee A.
    Background: Genistein is one among the several other known isoflavones that is found in different soybeans and soy products. The chemical name of genistein is 4?,5,7-trihydroxyisoflavone. Genistein has drawn attention of scientific community because of its potential beneficial effects on human grave diseases, such as cancer. Mechanistic insight of genistein reveals its potential for apoptotic induction, cell cycle arrest, as well as antiangiogenic, antimetastatic, and anti-inflammatory effects. Objective: The purpose of this review is to unravel and analyze various molecular mechanisms of genistein in diverse cancer models. Data sources: English language literature was searched using various databases, such as PubMed, ScienceDirect, EBOSCOhost, Scopus, Web of Science, and Cochrane Library. Key words used in various combinations included genistein, cancer, anticancer, molecular mechanisms prevention, treatment, in vivo, in vitro, and clinical studies. Study selection: Study selection was carried out strictly in accordance with the statement of Preferred Reporting Items for Systematic Reviews and Meta-analyses. Data extraction: Four authors independently carried out the extraction of articles. Data synthesis: One hundred one papers were found suitable for use in this review. Conclusion: This review covers various molecular interactions of genistein with various cellular targets in cancer models. It will help the scientific community understand genistein and cancer biology and will provoke them to design novel therapeutic strategies.
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    Identification of Curcuma longa phytochemicals as a novel inhibitor of proteins involved in Allergic Rhinitis
    (Central University of Punjab, 2018) Das, Swagata; Kumar, Shashank
    Histamine and other chemical mediators play crucial role in the disease development condition of allergic rhinitis. Allergic rhinitis is a mild or severe allergic condition due to the interaction of allergens with the IgE antibodies leading to release of chemical mediators like histamine, leukotrienes, prostaglandins etc. Various drug therapies have been elucidated based on the target proteins or enzymes involved. Certain specific proteins like histamine H1 receptor (3rze), histidine decarboxylase (4e1o), leukotriene C4 synthase (3hkk), 5-lipoxygenase (3o8y) alongwith non specific proteins like adenylate kinase (2c9y), phospholipase C (4qj4) are mainly targeted. Commonly prescribed drugs are antihistamines and leukotriene receptor antagonists, which generally reduces the symptoms occurring due to the release of the chemical mediators. Yet, there are persistent and prevalent conditions whereby the release and accumulation of histamine is misinterpreted as allergy instead of a totally different condition called histamine intolerance resulting in histamine accumulation due to defected or mutated enzymes related in its metabolism. Now days natural products are popular remedies against a number of diseases and allergic rhinitis is no exception. These products have been significantly reported due to the low/non-toxicity and cost effectiveness. Curcuma longa or turmeric is a common medicinal herb with iv enormous medicinal properties including anti-inflammatory properties. Various phytoconstituents of turmeric were identified and considered for receptor-based molecular docking. The target proteins and their interactions with each of phytoconstituent present in turmeric were studied.
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    In Silico and In Vitro Studies Evidenced Anticancer Natural Compounds, a Targeting Chemokine Receptor
    (iMedPub, 2016) Singh, Pushpendra; Bast, Felix
    Chemokines are a family of small chemotactic cytokines, which play a significant role in lymphocyte homing to secondary lymphoid organs in addition to tumor growth and metastasis. Thus, inhibition of chemokine receptor caught attention for anticancer treatment strategy. We studied molecular docking of chemokines receptor CXCR2, CXCR4, and CCR5 against natural and marine compounds. All selected natural and marine compounds were docked with the X-ray crystal structure of CXCR2, CXCR4, and CCR5 retrieved from the PDB by using Maestro 9.6. Molecular docking was executed by the XP (extra precision) mode of GLIDE. On the basis of Gscore and protein-ligand interactions, top-ranking compounds were outlined. The docking study carried out to summarize the various Gscore, hydrophobic, electrostatic bond, hydrogen bond, π-cation and π-π interactions and oversee the protein-ligand interactions. Moreover, effect of Epigallocatechin-3-gallate (EGCG) on biological activity such as mRNA expression (CXCR2, CCR5, and Bid), cell proliferation, ROS, and cell-migration was reported after the 48 hrs treatments in MCF-7 cells. The RT-PCR densitometric bands analysis showed that compound EGCG reduced the mRNA expression of CXCR2, CCR5 and increased the Bid at 40 μM and 80 μM concentration. Moreover, EGCG significantly reduced cell proliferation, ROS generation and cell-migration after 48 hours treatments.
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    Natural Compounds Targeting Transforming Growth Factor-β: In Silico and In Vitro Study
    (ejBio, 2016) Singh, Pushpendra; Bast, Felix; Singh, Ravi Shankar
    Inhibition of the tumor-promoting effects of transforming growth factor beta receptor (TGFβR) in carcinogenesis provides a better therapeutic intervention. Various natural compounds, inhibitors of TGFβR have been used for in vitro and in vivo anticancer study. Although very few TGFβR inhibitors are now intensifying in preclinical studies. In this study our aim to investigate TGFβR1, TGFβR2 and TAK1 inhibitor by using molecular docking and in vitro study. Our result revealed that some compounds have better docking energy. Moreover, the effect of two lead molecules epigallocatechin gallate (EGCG) and myricetin on the mRNA expression of TGFβR1 was reported after the 48 hrs treatments in HepG2 and PC3 cancer cell lines. The RT-PCR showed that compound EGCG and myricetin reduced the mRNA expression of TGFβR1 at 80 μM concentration. This molecular docking study provides a better understanding of binding of compounds to the active site of proteins and to summarize the various binding energy, hydrophobic, hydrogen, an electrostatic bond that are decisive for the protein-ligand interactions. Further experimental work will be required for validation of our results.