Department Of Botany
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Item Legume lectins: Potential use as a diagnostics and therapeutics against the cancer(Elsevier B.V., 2020) Gautam A.K.; Sharma D.; Sharma J.; Saini K.C.Legume lectins are carbohydrate-binding protein and widely distributed in a variety of species of leguminous plants and have drawn increased attention toward cancer. Nowadays, the lectins have been studied for the screening of potential biomarkers which increased its importance in cancer research. Few plant lectins have been shown to destroy cancer cells, suggesting that lectins may have biological potential in cancer treatments. In this review, we present a focused outline of legume lectins in descriptive their complex anti-cancer mechanisms on the bases of their properties of recognition and interacting specifically with carbohydrates binding sites. Existing reports suggested the binding of lectins to cancerous cells with their cell surface markers speculated by histochemistry in vitro and in vivo. In this review, we illuminate the use of legume lectins as a natural source for diagnostics and therapeutics purpose against cancer.Item Caulerpa taxifolia inhibits cell proliferation and induces oxidative stress in breast cancer cells(De Gruyter, 2019) Mehra R.; Bhushan S.; Yadav U.P.; Bast F.; Singh S.Caulerpa taxifolia (M. Vahl) C. Agardh or killer alga is known to possess several bioactive secondary metabolites with unique structural modifications. We investigated anti-oxidant and anti-proliferative activity of C. taxifolia extract (CTE) on breast and lung cancer cells, along with possible effects on mitochondrial membrane potential (MMP) and cell cycle progression. The results revealed up to 6-folds increase in reactive oxygen species (ROS), 2-folds increase in glutathione reductase (GR) activity, 1.7-fold increase in superoxide dismutase (SOD) activity and 1.8-fold change in catalase activity w.r.t. untreated cells i.e. 10.72 to 21.44 nmol/min/mL, 2.0 to 3.49 U/mL and 37.51 to 69.26 U/min/g FW, respectively, in MDA-MB-cells. Likewise, selective anti-proliferative activity with IC50 0.19 + 0.1, 0.27 + 0.1, and 0.43 + 0.1 μg/μL, was recorded in MDA-MB-231, T-47D, and H1299 cells. In addition, dose-dependent increase in MMP of up to 40% and G1/S phase mitotic arrest was documented by CTE treatment in MDA-MB-231 cells. The results suggest an anti-proliferative and oxidative stress inducing activity of CTE. Changes in MMP and cell cycle arrest further support the anti-cancer effects of CTE. It is believed that C. taxifolia may be considered as a potent source of anti-cancer drugs, subject to further validations.Item Antioxidant potential of ganoderic acid in Notch-1 protein in neuroblastoma(Springer New York LLC, 2019) Gill B.S.; Navgeet; Kumar S.Neuroblastoma is a childhood tumor arising from developing a sympathetic nervous system and causes around 10% of pediatric tumors. Despite advancement in the use of sophisticated techniques in molecular biology, neuroblastoma patient's survivability rate is very less. Notch pathway is significant in upholding cell maintenance and developmental process of organs. Notch-1 proteins are a ligand-activated transmembrane receptor which decides the fate of the cell. Notch signaling leads to transcription of genes which indulged in numerous diseases including tumor progression. Ganoderic acid, a lanosterol triterpene, isolated from fungus Ganoderma lucidum with a wide range of medicinal values. In the present study, various isoforms of the ganoderic acid and natural inhibitors were docked by molecular docking using Maestro 9 in the Notch-1 signaling pathway. The receptor-based molecular docking exposed the best binding interaction of Notch-1 with ganoderic acid A with GScore (? 8.088), kcal/mol, Lipophilic EvdW (? 1.74), Electro (? 1.18), Glide emodel (? 89.944) with the active participation of Arg 189, Arg 199, Glu 232 residues. On the other hand natural inhibitor, curcumin has GScore (? 7.644), kcal/mol, Lipophilic EvdW (? 2.19), Electro (? 0.73), Glide emodel (? 70.957) with Arg 75 residues involved in docking. The ligand binding affinity of ganoderic acid A in Notch-1 is calculated using MM-GBSA (? 76.782), whereas curcumin has (? 72.815) kcal/mol. The QikProp analyzed the various drug-likeness parameters such as absorption, distribution, metabolism, excretion, and toxicity (ADME/T) and isoforms of ganoderic acid require some modification to fall under Lipinski rule. The ganoderic acid A and curcumin were the best-docked among different compounds and exhibits downregulation in Notch-1 mRNA expression and inhibits proliferation, viability, and ROS activity in IMR-32 cells.Item Molecular docking and in vitro study of Syzygium cumini-derived natural compounds on receptor tyrosine kinases pathway components(Inderscience Enterprises Ltd., 2019) Singh, P; Bast, Felix; Bhushan, S; Mehra, R; Kamboj, P.Syzygium cumini (S. cumini) is used for a variety of biological activities such as anti-inflammatory, anti-diabetic and anti-oxidant; currently, it has been reported for DNA protecting activity against radiation damage. Receptor tyrosine kinases (RTKs) are identified as critical regulators of various cellular processes including cell proliferation, metabolism and apoptosis. These receptors have recently gained attention as an attractive target for cancer treatment. The present research was aimed to screen S. cumini-derived natural compounds against RTKs pathway components using molecular docking. Furthermore, in vitro anti-proliferative 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and anti-oxidative (nitro blue tetrazolium and H 2 CDFD) activities of leaf extract of S. cumini are also reported. Selected natural compounds were docked with X-ray crystal structure of RTKs signalling proteins using grid-based ligand docking with energetics Maestro 9.6. In the present investigation, our result highlighted that myricetin, kaempferol, delphinidin chloride, ellagic acid, rutin, petunidin, gossypol and mirtillin generated a good dock score with all selected proteins. Protein-ligand interactions accentuated that several bonds such as lipophilic, hydrogen bonding, π-π stacking and cation-π interactions represent a ruling contribution at the active site. Moreover, reduction in cell viability with leaf extract of S. cumini treatment at concentrations of 5-80 µg/ml after 48 h in MCF-7 cells was observed. Leaf extract of S. cumini significantly reduced the Reactive oxygen species (ROS) generation in MCF-7 cells after 48 h. These results indicate the anti-cancer potential of S. cumini. Thus, isolation and purification of anti-cancerous compounds are suggested to explore more possibilities in the field. © 2019 Inderscience Enterprises Ltd.Item Marine macroalga Caulerpa: role of its metabolites in modulating cancer signaling(Springer, 2019) Mehra, R; Bhushan, S; Bast, Felix; Singh, S.Cancer, the leading causes of death worldwide, causes multiple metabolic and physiological alterations, leading to an unregulated proliferation of cells. The existing anticancer therapies are usually nonspecific with side effects and or are extremely expensive, thus hunt for better therapeutics is still on, specially efforts are made to look for naturally occurring molecules. Sea harbors several organisms which are unexplored for their biological potentials. Green macroalga genus, Caulerpa, is one such invaluable repository of bioactive metabolites like alkaloids, terpenoids, flavonoids, steroids and tannins with reported bioactivities against many diseases including cancer. Anti-cancerous metabolites of Caulerpa like caulerpenyne (Cyn), caulerpin, caulersin, and racemosin C, possess unique structural moieties and are known to exhibit distinct effects on cancer cells. Theses metabolites are reported to affect microtubule dynamics, unfolded protein response, mitochondrial health, cell cycle progression, metabolic and stress pathways by their cross-talk with signalling proteins like AMPK, GRP78, GADD153, Bid, Bax, AIF, Bcl2, P21, cyclin D, cyclin E, caspase 9, and PTP1B. Targeting of multiple cancer hallmarks by Caulerpa metabolites, with concomitant modulations of multiple signalling cascades, displays its multifactorial approach against cancer. Evaluation of anti-cancer properties of this genus is particularly important as Caulerpa species are widely edible and utilized in several delicacies in the coastal countries. This is the first review article providing a consolidated information about the role of Caulerpa in cancer with major contributing metabolites and plausible modulations in cancer signaling and prospects. © 2019, Springer Nature B.V.Item Natural products as multidrug resistance modulators in cancer(Elsevier, 2019) Kumar, Amit; Jaitak, VikasCancer is a prominent cause of death globally. Currently, many drugs that are in clinical practice are having a high prevalence of side effect and multidrug resistance. Risk of tumors acquiring resistance to chemotherapy (multidrug resistance) remains a significant hurdle to the successful treatment of various types of cancer. Membrane-embedded drug transporters, generally overexpressed in cancer, are the leading cause among multiple mechanisms of multidrug resistance (MDR). P-glycoprotein (P-gp) also MDR1/ABCB1, multidrug resistance associated protein 1 (MRP1/ABCC1), MRP2 and breast cancer resistance protein (BCRP/ABCG2) are considered to be a prime factor for induction of MDR. To date, several chemical substances have been tested in a number of clinical trials for their MDR modulatory activity which are not having devoid of any side effects that necessitates to find newer and safer way to tackle the current problem of multidrug resistance in cancer. The present study systematically discusses the various classes of natural products i.e flavonoids, alkaloids, terpenoids, coumarins (from plants, marine, and microorganisms) as potential MDR modulators and/or as a source of promising lead compounds. Recently a bisbenzyl isoquinoline alkaloid namely tetrandrine, isolated from Chinese herb Stephania tetrandra (Han-Fang-Chi) is in clinical trials for its MDR reversal activity. © 2019 Elsevier Masson SASItem Insilco Molecular Docking Study of Natural Compounds On Wild and Mutated Epidermal Growth Factor Receptor(Springer, 2014) Singh, Pushpendra; Bast, FelixThe role played by overexpression of tyrosine kinase epidermal growth factor receptor (EGFR), the transmembrane receptor central to numerous cellular processes comprising cell migration, adhesion, apoptosis, and cell proliferation, has been highlighted in various cancers such as prostate, breast, lung, and ovarian cancers as well as in mutations in the EGFR kinase domain. Although many therapeutic approaches have targetted EGFR, the mutations occurring in the EGFR kinase domain including L858 EGFR and T790/L858R had led to the amplification of EGFR signals, consequently leading to increased cell proliferation and cell growth. The strategies involving the inhibition of EGFR L858 and T790M have been accredited with limited achievement in addition to being associated with unwanted adverse effects as a result of crosstalk of wild-type EGFR. All current EGFR tyrosine kinase inhibitors have been identified as ATP competitive inhibitors of wild-type EGFR possessing aniline and quinazoline moiety on the ligands skeleton. Our results obtained by performing molecular docking study on Maestro 9.3 molecular docking suite indicated that CID5280343 possesses better energy conformation against wild-type EGFR as well as two mutated EGFR. Moreover, it was discovered in this study that the natural compounds CID72276, CID5280445, CID441794, and CID72277 and InterBioScreen's library STOCK1N-78657, STOCK1N-78976, and STOCK1N-78847 have better binding conformation against gatekeeper T790M mutated EGFR concluded to be brought about by means of flexible ligands/receptor-based molecular docking protocol. Miraculous features of these compounds are their various pharmacokinetic and pharmacodynamic parameters which were found to be satisfactory as drug-like molecules. This molecular docking study also summarizes docking free energy, protein-ligands interaction profile, and pharmacokinetic and pharmacodynamic parameter of lead molecules which were tremendously helpful in enhancing the activity of these natural compounds against EGFR.Item Caulerpa taxifolia inhibits cell proliferation and induces oxidative stress in breast cancer cells(Springer, 2018) Mehra, Richa; Bhushan, Satej; Yadav, Umesh Prasad; Bast, Felix; Singh, SandeepCaulerpa taxifolia (M. Vahl) C. Agardh or killer alga is known to possess several bioactive secondary metabolites with unique structural modifications. We investigated anti-oxidant and anti-proliferative activity of C. taxifolia extract (CTE) on breast and lung cancer cells, along with possible effects on mitochondrial membrane potential (MMP) and cell cycle progression. The results revealed up to 6-folds increase in reactive oxygen species (ROS), 2-folds increase in glutathione reductase (GR) activity, 1.7-fold increase in superoxide dismutase (SOD) activity and 1.8-fold change in catalase activity w.r.t. untreated cells i.e. 10.72 to 21.44 nmol/min/mL, 2.0 to 3.49 U/mL and 37.51 to 69.26 U/min/g FW, respectively, in MDA-MB-cells. Likewise, selective anti-proliferative activity with IC50 0.19 + 0.1, 0.27 + 0.1, and 0.43 + 0.1 μg/μL, was recorded in MDA-MB-231, T-47D, and H1299 cells. In addition, dose-dependent increase in MMP of up to 40% and G1/S phase mitotic arrest was documented by CTE treatment in MDA-MB-231 cells. The results suggest an anti-proliferative and oxidative stress inducing activity of CTE. Changes in MMP and cell cycle arrest further support the anti-cancer effects of CTE. It is believed that C. taxifolia may be considered as a potent source of anti-cancer drugs, subject to further validations.Item Vitex negundo and its medicinal value(Springer, 2018) Gill, Balraj Singh; Mehra, Richa; Navget; Kumar, SanjeevNatural products are rich in several potent bioactive compounds, targeting complex network of proteins involved in various diseases. Vitex negundo (VN), commonly known as “chaste tree”, is an ethnobotanically important plant with enormous medicinal properties. Different species of Vitex vary in chemical composition, thus producing different phytochemicals. Several bioactive compounds have been extracted from leaves, seeds, roots in form of volatile oils, flavonoids, lignans, iridoids, terpenes, and steroids. These bioactive compounds exhibit anti-inflammatory, antioxidant, antidiabetic, anticancer, antimicrobial. VN is typically known for its role in the modulation of cellular events like apoptosis, cell cycle, motility of sperms, polycystic ovary disease, and menstrual cycle. VN, reportedly, perturbs many cancer-signaling pathways involving p-p38, p-ERK1/2, and p-JNK in LPS-elicited cells, N-terminal kinase (JNK), COX-1 pathways, MAPK, NF-κB, tumor necrosis factor α (TNF-α), Akt, mTOR, vascular endothelial growth factor, hypoxia-inducible factor (HIF-1α). Several bioactive compounds obtained from VN have been commercialized and others are under investigation. This is the first review presenting up-to-date information about the VN, its bioactive constituents and their mode of action.Item Antioxidant potential of ganoderic acid in Notch-1 protein in neuroblastoma(Springer, 2018) Gill, Balraj Singh; Navgeet; Kuamr, SanjeevNeuroblastoma is a childhood tumor arising from developing a sympathetic nervous system and causes around 10% of pediatric tumors. Despite advancement in the use of sophisticated techniques in molecular biology, neuroblastoma patient's survivability rate is very less. Notch pathway is significant in upholding cell maintenance and developmental process of organs. Notch-1 proteins are a ligand-activated transmembrane receptor which decides the fate of the cell. Notch signaling leads to transcription of genes which indulged in numerous diseases including tumor progression. Ganoderic acid, a lanosterol triterpene, isolated from fungus Ganoderma lucidum with a wide range of medicinal values. In the present study, various isoforms of the ganoderic acid and natural inhibitors were docked by molecular docking using Maestro 9 in the Notch-1 signaling pathway. The receptor-based molecular docking exposed the best binding interaction of Notch-1 with ganoderic acid A with GScore (- 8.088), kcal/mol, Lipophilic EvdW (- 1.74), Electro (- 1.18), Glide emodel (- 89.944) with the active participation of Arg 189, Arg 199, Glu 232 residues. On the other hand natural inhibitor, curcumin has GScore (- 7.644), kcal/mol, Lipophilic EvdW (- 2.19), Electro (- 0.73), Glide emodel (- 70.957) with Arg 75 residues involved in docking. The ligand binding affinity of ganoderic acid A in Notch-1 is calculated using MM-GBSA (- 76.782), whereas curcumin has (- 72.815) kcal/mol. The QikProp analyzed the various drug-likeness parameters such as absorption, distribution, metabolism, excretion, and toxicity (ADME/T) and isoforms of ganoderic acid require some modification to fall under Lipinski rule. The ganoderic acid A and curcumin were the best-docked among different compounds and exhibits downregulation in Notch-1 mRNA expression and inhibits proliferation, viability, and ROS activity in IMR-32 cells.