Botany - Research Publications
Permanent URI for this collectionhttps://kr.cup.edu.in/handle/32116/32
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Item Triterpenes in cancer: significance and their influence(Springer Netherlands, 2016) Gill, Balraj Singh; Kumar, Sanjeev; NavgeetNatural products are enriched with numerous compounds with a broad spectrum of therapeutics indication suggesting the role of functional moieties as a core pharmacophore. This review highlights the role of triterpene in targeting signaling pathways in cancer. Advancement in cellular, biochemical, experimental, and computational approaches provides new insights into various pathways in cancer. In signaling network, triterpenes primarily target membrane receptors which control and modulates expression level of the biological responses. Triterpenes are immunomodulatory targeting nuclear factor kappa B, toll-like receptors, signal transducer and activator of transcription 3, and PI3K/Akt/mTOR. Triterpenes isolated from plants and fungus mainly focus on the process of apoptosis while other signaling areas in the cancer are still shrouded. Some of the triterpenes have already passed the clinical trial, whereas many more have been proven to yield effective results. This review would help the researchers to study the role of triterpenes in cancer, thus, helping them to discover and design efficacious therapeutics agents. ? 2016, Springer Science+Business Media Dordrecht.Item Missing link between microRNA and prostate cancer(Springer Netherlands, 2016) Gill, Balraj Singh; Alex, Jimi Marin; Navgeet; Kumar, Sanjeev; Gill, B.S.; Alex, J.M.; Navgeet, Kumar, S.MicroRNAs are the non-coding RNAs which regulate endogenous gene expression in animal and plant cells. Alterations in the level of micro-ribonucleic acids (miRNAs) involving the deletions, overexpression, mutations, epigenetic silencing, or dysregulation of transcription factors that target specific miRNAs may culminate in various diseases including cancer. Recent findings demonstrate the role of miRNAs in prostate cancer. Numerous discoveries of miRNAs have marked the research and development surrounding prostate cancer management, diagnosis, and therapy which has made prediction easy, but the effective treatment strategy remains a mystery. This review seeks to draw a link between miRNA and prostate cancer through an understanding of the numerous signaling pathways that these miRNAs control, which may prove to be helpful in identifying therapeutically interesting molecular targets. ? 2016, International Society of Oncology and BioMarkers (ISOBM).Item Misconstrued versatility of Ganoderma lucidum: a key player in multi-targeted cellular signaling(Springer, 2016) Gill, Balraj Singh; Sharma, Prateek; Kumar, Raj; Kumar, SanjeevA Basidiomycetes fungus belonging to polypore family of mushrooms, Ganoderma lucidum (GL), has been known since a long time for their myriad therapeutic indications. Renowned as an invaluable resource of cardinal mycoconstituents they encompass numerous terpenoids polysaccharides and proteins. Possessing the therapeutically potent lanosteroidal skeleton, terpenoids are upheld for their invariable participation in therapeutically diverse bioactivities. Polysaccharides and proteins exhibiting distinguishable bioactivities provide this oriental mushroom with additional edges over immune function and anti-cancer potential. This review is a concerted effort to throw light upon the therapeutic versatility of the fungus, shadowed by various other natural products. An effort has been made towards conglomerating the mycoconstituents decisive for the many activities portrayed by this fungus. More importantly, this review seeks to fathom the inextricable role played by derivatives in modulating signaling cascades such as downregulation of various mitogenic pathways, inhibiting growth factors, or upregulating certain pathways enhancing cellular integrity.Item Ganoderma lucidum targeting lung cancer signaling: A review(SAGE Publications Ltd, 2017) Gill, Balraj Singh; Navgeet; Kumar, Sanjeev; Gill, B.S.; Navgeet, Kumar, S.Lung cancer causes huge mortality to population, and pharmaceutical companies require new drugs as an alternative either synthetic or natural targeting lung cancer. The conventional therapies cause side effects, and therefore, natural products are used as a therapeutic candidate in lung cancer. Chemical diversity among natural products highlights the impact of evolution and survival of fittest. One such neglected natural product is Ganoderma lucidum used for promoting health and longevity for a longer time. The major bioconstituents of G. lucidum are mainly terpenes, polysaccharides, and proteins, which were explored for various activities ranging from apoptosis to autophagy. The bioconstituents of G. lucidum activate plasma membrane receptors and initiate various downstream signaling leading to nuclear factor-?B, phosphoinositide 3-kinase, Akt, and mammalian target of rapamycin in cancer. The bioconstituents regulate the expression of various genes involved in cell cycle, immune response, apoptosis, and autophagy in lung cancer. This review highlights the inextricable role of G. lucidum and its bioconstituents in lung cancer signaling for the first time. ? The Author(s) 2017.Item Ganoderic acid targeting multiple receptors in cancer: in silico and in vitro study(Springer Netherlands, 2016) Gill, Balraj Singh; Navgeet; Kumar, Sanjeev; Gill, B.S.; Navgeet, Kumar, S.Receptor tyrosine kinases (RTKs) are transmembrane high-affinity surface receptors responsible for cell migration, adhesion, apoptosis, metabolism, and cell proliferation activities in various cancers. Minute aberration in the RTK signaling modulates the downstream signaling pathways that results in cancer. Ganoderic acid is a triterpene isolated from Ganoderma lucidum, which is renowned for its therapeutics effect, especially in cancer. The present study discusses receptor-based molecular docking of insulin receptor (IR), insulin-like growth factor receptor 1 (IGFR-1), vascular endothelial growth factor receptor-1 (VEGFR-1), vascular endothelial growth factor receptor-2 (VEGFR-2), and estrogen receptor (ER) with 50 isoforms of ganoderic acid along with natural inhibitors. These receptors were assessed for toxicity (ADMET) by using Maestro 9.6 (Schr?dinger Inc). The calculated docking free energy yielded an excellent dock score for the ganoderic acid when docked with proteins IR, IGFR-1, VEGFR-1, VEGFR-2, and ER, suggesting its potential in combating cancer. Protein?ligand profile highlighted the binding interactions comprising lipophilic, hydrogen bonding, pi-pi stacking interactions, and noncovalent bonding which play a pivotal role in targeting cancer. In silico studies revealed structure of ganoderic acid A as best isoforms among 50 isoforms which exhibits biological activity in liver cancer cells. Ganoderic acids A significantly decrease the viability, proliferation, and oxidative stress in a dose-dependent manner in liver cancer cells. ? 2016, International Society of Oncology and BioMarkers (ISOBM).Item Ganoderic acid targeting nuclear factor erythroid 2–related factor 2 in lung cancer(Sage, 2017) Gill, Balraj Singh; Kumar, Sanjeev; NavgeetLung cancer causes huge mortality worldwide, and targeting new pathway may provide an alternative in modulating signaling in cancer. Nuclear factor erythroid 2–related factor 2 is the major regulator of endogenous and exogenous stress by activating numerous antioxidant genes critical in cancer, Alzheimer’s, Parkinson’s, and inflammatory bowel diseases. Ganoderic acid is a triterpene from basiodiomycetes fungus Ganoderma lucidum with numerous therapeutic effects. In this study, ganoderic acid and its 50 isomers and natural activators were docked by receptor-based molecular docking using Maestro 9.6 (Schrödinger Inc.) in the Kelch-like ECH-associated protein 1-nuclear factor erythroid 2–related factor 2 signaling pathway. The receptor-based molecular docking reveals the best binding interaction of nuclear factor erythroid 2–related factor 2 and ganoderic acid A with GScore (−9.69) (kcal/mol), Lipophilic EvdW (−1.83), Electro (−0.72), Glide emodel (−73.369), H bond (−1.1), molecular mechanics/generalized Born surface area (−75.541) with Leu 718, Asp 800, Cys 797 residues involved in hydrogen bonding. The calculated docking energy highlights the lipophilic, hydrogen bonding, pi–pi stacking interactions, and non-covalent bonding. Analysis showed the involvement of cysteine and serine residues which were crucial in the activation and translocation from cytoplasm to the nucleus in the nuclear factor erythroid 2–related factor 2 signaling process. The molecular docking tool QikProp analyzed the absorption, distribution, metabolism, excretion, and toxicity but needs some modifications in their structure to satisfy Lipinski’s rule. Ganoderic acid A is a best docked isoform which inhibits the cell proliferation, viability, migration, and reactive oxygen species and messenger RNA expression of nuclear factor erythroid 2–related factor 2 in H460 cells.Item Ganoderic acid modulating TNF and its receptors: in silico and in vitro study(Springer, 2017) Gill, Balraj Singh; Navgeet; Kumar, SanjeevCancer is a multifactorial disease with a network of genes causing genetic alterations. The sophisticated techniques in molecular biology revealed different cancer pathway, but their mechanistic approach is still shrouded. Tumor necrosis factor and TNF-related apoptosis-inducing ligand receptors (DR5) emerged as potential target drug for the cancer therapy. Among natural products basidiomycete fungus, Ganoderma lucidum and its constituents endowed with a plethora of activities modulating signaling in cancer. Ganoderic acid, a triterpene with lanosteroidal skeleton play an inextricable role in modulating signaling cascades in various mitogenic pathways. In the present study, receptor-based molecular docking was performed to study the dynamic behavior of the docked complexes and the molecular interactions between ganoderic acid and its isoforms with tumor necrosis factor and its receptor (DR5). The top scoring compounds were compared with the already documented natural inhibitor of tumor necrosis factor, DR5-curcumin, catechin, bupropion, pentoxyphyllin for their binding affinity and other absorption, distribution, metabolism, excretion, and toxicity properties. Ganoderic acid A interact more promising as compared with other isoforms with GScore (−9.858 (kcal/mol), Lipophilic EvdW (−1.7), H Bond (−0.9), Glide emodel (−40.5) with the involvement of Tyr 151, Leu 120 and Gln 149 residues during binding with tumor necrosis factor. During docking of ganoderic acid with DR5, ganoderic acid A exhibits GScore (−8.7), HBond (−2.9), Glide emodel (−30.0) with the involvement of hydrogen bonding inMet99, Arg101, Pro97, Glu98 residues. Natural inhibitors already documented exhibit low-binding energy and other docking parameters, which have an edge of ganoderic acid A to tumor necrosis factor and DR5. Ganoderic acid A efficiently inhibits the proliferation, viability, and intracellular reactive oxygenItem Ganoderic Acid A Targeting β-Catenin in Wnt Signaling Pathway: In Silico and In Vitro Study(Springer, 2016) Gill, Balraj Singh; Kumar, Sanjeev; NavgeetWnt signaling pathways are the group of signaling transduction controlling the embryonic development, cell proliferation, cell migration, cell fate specification, and body axis pattern. Nuclear accumulation of β-catenin in Wnt signaling is a widely recognized marker of poor cancer prognosis which regulates fat and glucose metabolism. Ganoderic acid is a triterpene isolated from fungus Ganoderma lucidum renowned for its pharmacological effects. The present study revealed the mechanistic study of β-catenin with 50 isoforms of ganoderic acid by molecular docking using Maestro 9.6 (Schrödinger Inc) in Wnt signaling pathway. Molecular docking reveals the binding interaction of β-catenin and ganoderic acid A with GScore (−9.44), kcal/mol, lipophilic EvdW (−2.86), electro (−0.72), Glide emodel (−50.401), MM-GBSA (−87.441), H bond (−1.91) with Lys 180 and Asn 220 residues involved in hydrogen bonding. Qikprop analyzed the absorption, distribution, metabolism, excretion, and toxicity and confirmed that most of the isoforms satisfies Lipinski rule but needs little modifications in their structure. The ganoderic acid A is the best-docked isoforms which inhibits the proliferation, viability, and intracellular ROS of pancreatic cancer RIN-5F cells in a dose-dependent manner.Item Evaluating anti-oxidant potential of ganoderic acid A in STAT 3 pathway in prostate cancer(Springer Netherlands, 2016) Gill, Balraj Singh; Kumar, Sanjeev; NavgeetEvaluating anti-oxidant potential of Ganoderic acid A in STAT 3 pathway in Prostate cancer. Molecular docking and ADMET activities of different isoforms of ganoderic acid on STAT 3 pathway were performed by Maestro 9.6 (Schr�dinger Inc). The ganoderic acid A is best-docked among isoforms which analyses the expression level of antioxidant and STAT 3 pathway in PC-3 cells. The receptor-based molecular docking reveals the best binding interaction of SH2 domain of STAT3 and ganoderic acid A with GScore (?6.134), kcal/mol, Lipophilic EvdW (?1.83), Electro (?1.1), Glide emodel (?31.857), H bond (1.98), MM-GBSA (?69.555). The molecular docking QikProp analyzed the absorption, distribution, metabolism, excretion, and toxicity (ADME/T). The ganoderic acid A is best-docked among isoforms which downregulates the expression of STAT 3 in PC-3 cells. Moreover, ganoderic acid A inhibits proliferation, viability, ROS, DPPH, and analyzed the expression of SOD1, SOD2, and SOD3 by Real time PCR in a PC-3 cell in a dose-dependent manner. Molecular docking revealed the mechanistic binding of Ganoderic acid A in STAT3 signaling, which inhibits the proliferation, viability, and ROS in PC-3 cells. � 2016, Springer Science+Business Media Dordrecht.Item Differential algorithms-assisted molecular modeling-based identification of mechanistic binding of ganoderic acids(Springer, 2015) Gill, Balraj Singh; Kumar, SanjeevGanoderma, in the recent years, has been comprehensively characterized and held invaluable for their miscellaneous pharmacological activities. Recently, attempts to explore and fathom the pathway of inhibition revealed GA-A and GA-H to impede the progression of breast cancer by inhibiting the signaling of AP-1 and NF-κB, although the mechanism has not yet been explored. NF-κB is a key transcription factor having irrefutable role in cell proliferation, apoptosis and cancer signaling and its subunits κB-IKKα, IKKβ and IKKγ (NEMO) are pivotal to the cancer signaling mechanism. The present study confirmed mechanistically the association between NF-κB and NEMO in regulating the signaling cascade of NF-κB. GA-A and GA-H were observed to participate in various non-covalent interactions, thus contributing largely to the stability of the ligand–macromolecules association as well as their role as anticancer agent in breast cancer. Amino acids, Lys90 and Asn732, were seen to be critically involved in the signaling cascade. Apart from this, residues Glu98 and Met94, Cys95 and Glu91 were involved in hydrogen bonding in GA-A and GA-H. The anticancer activity exhibited by GA-A and GA-H is attributed to certain docking poses and interaction that were found to be absent in the GA-F such as hydroxylation at 3 and 7 and/or 15 in the lanostane structure. This study is the first of its kind elucidating a possible mode of binding of ganoderic acid in NF-κB signaling pathway using molecular modeling studies, further evaluated by differential calculation-based algorithms.