School Of Basic And Applied Sciences

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    Emerging role of ZBTB7A as an oncogenic driver and transcriptional repressor
    (Elsevier, 2020) Gupta, S; Singh, A.K; Prajapati, K.S; Kushwaha, P.P; Shuaib, M; Kumar, S.
    ZBTB7A is a member of the POK family of transcription factors that possesses a POZ-domain at the N-terminus and Krüppel-like zinc-finger at the c-terminus. ZBTB7A was initially isolated as a protein that binds to the inducer of the short transcript of HIV-1 virus TAT gene promoter. The protein forms a homodimer through protein-protein interaction via the N-terminus POZ-domains. ZBTB7A typically binds to the DNA elements through its zinc-finger domains and represses transcription both by modification of the chromatin organization and through the direct recruitment of transcription factors to gene regulatory regions. ZBTB7A is involved in several fundamental biological processes including cell proliferation, differentiation, and development. It also participates in hematopoiesis, adipogenesis, chondrogenesis, cellular metabolism and alternative splicing of BCLXL, DNA repair, development of oligodendrocytes, osteoclast and unfolded protein response. Aberrant ZBTB7A expression promotes oncogenic transformation and tumor progression, but also maintains a tumor suppressive role depending on the type and genetic context of cancer. In this comprehensive review we provide information about the structure, function, targets, and regulators of ZBTB7A and its role as an oncogenic driver and transcriptional repressor in various human diseases. - 2020 Elsevier B.V.
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    Molecular mechanisms of action of tocotrienols in cancer: Recent trends and advancements
    (MDPI AG, 2019) Aggarwal, V; Kashyap, D; Sak, K; Tuli, H.S; Jain, Aklank; Chaudhary, A; Garg, V.K; Sethi, G; Yerer, M.B.
    Tocotrienols, found in several natural sources such as rice bran, annatto seeds, and palm oil have been reported to exert various beneficial health promoting properties especially against chronic diseases, including cancer. The incidence of cancer is rapidly increasing around the world not only because of continual aging and growth in global population, but also due to the adaptation of Western lifestyle behaviours, including intake of high fat diets and low physical activity. Tocotrienols can suppress the growth of different malignancies, including those of breast, lung, ovary, prostate, liver, brain, colon, myeloma, and pancreas. These findings, together with the reported safety profile of tocotrienols in healthy human volunteers, encourage further studies on the potential application of these compounds in cancer prevention and treatment. In the current article, detailed information about the potential molecular mechanisms of actions of tocotrienols in different cancer models has been presented and the possible effects of these vitamin E analogues on various important cancer hallmarks, i.e., cellular proliferation, apoptosis, angiogenesis, metastasis, and inflammation have been briefly analyzed. © 2019 by the authors. Licensee MDPI, Basel, Switzerland.
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    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.
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    Natural products as multidrug resistance modulators in cancer
    (Elsevier, 2019) Kumar, Amit; Jaitak, Vikas
    Cancer 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 SAS
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    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, Sandeep
    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.
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    Vitex negundo and its medicinal value
    (Springer, 2018) Gill, Balraj Singh; Mehra, Richa; Navget; Kumar, Sanjeev
    Natural 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.
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    Antioxidant potential of ganoderic acid in Notch-1 protein in neuroblastoma
    (Springer, 2018) Gill, Balraj Singh; Navgeet; Kuamr, Sanjeev
    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.
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    Synthesis and In Silico Studies Of Quinazolinone Derivatives As PARP-1 INHIBITORS
    (Central University of Punjab, 2018) Verma, Sonia; Kumar,Pradeep
    Cancer is one of the leading diseases responsible for high mortality rates worldwide. It develops when normal cells begin to grow out of control in particular part of the body. Cancer is a leading cause of death worldwide, accounting for 8.8 million deaths in 2015. According to WHO, the most common causes of cancer death are cancers of Lung (1.69 million deaths), Liver (788 000 deaths), Colorectal (774 000 deaths), Stomach (754 000 deaths) and Breast (571 000 deaths). PARP-1 is a ubiquitous zincfinger DNA-binding enzyme that is activated by binding to DNA breaks and then catalyzes the synthesis of the branched polymer PAR using NAD+ as the building block. PARP-1 has a crucial role in cell proliferation, survival, and death, due to its properties on regulation of multiple biological processes. Quinazolinone and its derivatives possess a large class of biologically active compounds that exhibited broad spectrum of biological activities such as anti-HIV, anticancer, antifungal, antibacterial, anticonvulsant, anti-inflammatory, antidepressant, antimalarial, antioxidant, antileukemic, and antileishmanial activities and other activities. In this study, we have synthesized quinazolinone derivatives and studied the in silico properties as PARP-1 inhibitors which indicated that quinazolinone derivatives were having good affinity towards active site of PARP-1. Out of all synthesized compounds, SVA-11 was having maximum dock score (-10.421).
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    Impact of mitochondrial transplantation on cancer cells
    (Central University of Punjab, 2014) Aggarwal, Alza; Bhardwaj, Pankaj
    Mitochondria, the powerhouse of the cell, are small granular or filamentous bodies associated significantly with cellular respiration and are the main sources of energy, due to which they are present in maximum number in the organs that require large amounts of energy for doing their function like muscle cells, neural cells, etc. In case of any dysfunction of mitochondria, these organs are most affected culminating in a number of serious multi organs diseases, irrespective of age such as neurogenic weakness with ataxia and retinitis pigmentosa (NARP), or Leigh syndrome (LS), Cancer, etc. Although mutations in mitochondrial genes are common in cancer cells, they do not inactivate mitochondrial energy metabolism, but rather alter the mitochondrial bioenergetics and biosynthetic state. Literature survey also revealed that owing to mitochondrial dysfunction the clinical trial of many anticancer drugs has failed in patients. This study is focused on the impact of mitochondrial transplantation on cancer cells and their drug sensitivity against four human cancer cell lines HCT116 (WT & P53mutated), HepG2 and MCF7. The normal cell's Mitochondria was transplanted into cancer cells and then evaluated the Impact of transplantation of mitochondria from healthy cells into cancer cell upon their growth, ROS production and their drug sensitivity. The results of this study revealed that the healthy mitochondria transplanted to cancer cells decrease carcinogenesis and have drug sensitivity. So, it may be used as futuristic cancer remedy.
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    Antiproliferative Activity of Chloroform and Methanol Extracts of Piper attenuatum (Buch-Ham)
    (Central University of Punjab, 2018) Pathak, Neha; Kumar, Raj
    Indian traditional medicinal plant Piper attenuatum (Buch-Ham) has been investigated for its antiproliferative activity. Dried powder of fruits of Piper attenuatum (Buch-Ham) was subjected to maceration to prepare various extracts using different solvents in the order of increasing polarity. In vitro antiproliferative activity of all the extract was carried out using MTT assay against MDA-MB-231(Breast cancer) cell line. The Chloroform and Methanol extracts were found to be the most active fractions. The results from MTT assay of isolated compounds from Chloroform extract, NP7C was found to be the most potent antiproliferative agent with IC50 value of 3.83 ?M which is comparable to etoposide 2.37 ?M. Compound NP7L also exhibit significant antiproliferative activity (IC50 of 6.44 ?M) which was comparable to colchicine (IC50 = 6.3 ?M). Thus, the present study indicated that isolated compounds of Piper attenuatum (Buch-Ham) possess great potential to be developed as anticancer agent in future.