Papers by Anupam Chatterjee
Genomics data, 2014
GST family genes have a critical role in xenobiotic metabolism and drug resistance. Among the GST... more GST family genes have a critical role in xenobiotic metabolism and drug resistance. Among the GST family the GST-μ, GST-π, GST-α and GST-θ are the most abundant classes and have a major role in the carcinogen detoxification process. Nevertheless the activity of these enzymes may differ due to polymorphisms which ultimately results in interindividual susceptibility to cancer development. In this work, we have analyzed the potentially deleterious nsSNPs that can alter the function of these genes. As a result among the nsSNPs, 101 (42.61%) were found to be deleterious by a sequence homology-based tool, 67 (28.27%) by a structure homology based tool and a total of 59 (24.89%) by both. We propose a modeled structure of the five highly deleterious mutant proteins. Our results will provide useful information in selecting target SNPs that are likely to have an impact on GST activity and contribute to an individual's susceptibility to the disease.
International Journal of Radiation Biology, 2007
To cite this Article Ray, S. and Chatterjee, A.(2007)'Influence of glutathione on the induction o... more To cite this Article Ray, S. and Chatterjee, A.(2007)'Influence of glutathione on the induction of chromosome aberrations, delay in cell cycle kinetics and cell cycle regulator proteins in irradiated mouse bone marrow cells',
Mutagenesis, 1998
Arecoline (ARC), an alkaloid of the betel nut (Areca catechu), is a major ingredient of betel qui... more Arecoline (ARC), an alkaloid of the betel nut (Areca catechu), is a major ingredient of betel quid. The carcinogenic potentiality as well as its cell transformation ability has already been reported. Reduced glutathione (GSH), a major non-protein thiol substance plays an important role in protection of cells against the toxic effect of exogenous compounds. In order to understand the role of factors which affect ARC sensitivity, we have made an attempt to establish a relationship between ARC-induced DNA damage and the endogenous GSH status of the cells. ARC was administered to untreated and buthionine sulfoximine (BSO) (a GSH-depleting agent)-treated mice. Exogenous GSH was also added to ARC-administered mice. Cells were fixed at 20 h and both chromosome aberrations (CAs) and sister chromatid exchanges (SCEs) were scored. Both CAs and SCEs were significantly induced by ARC and the frequency of both these parameters were increased further when ARC was given to BSO-treated mice. However, GSH reduced the frequency of CAs induced by ARC but failed to do so for SCEs. The data indicate that ARC-induced DNA damage is influenced by endogenous GSH level. The failure of GSH to reduce the frequency of SCEs indicates that the mechanism of induction of CAs and SCEs by ARC are different.
Clerodin (C24H34O7), a clerodane diterpenoid, is a bitter principle of Clerodendrum viscosum. The... more Clerodin (C24H34O7), a clerodane diterpenoid, is a bitter principle of Clerodendrum viscosum. The present study aimed to decipher colchicine-like actions of clerodin in terms of microtubule destabilization based mitotic abnormalities, G2-M arrest, and plant polyploidy. Purified clerodin showed increased metaphase frequency in Human Peripheral Blood Lymphocytes (HPBLs), Human Embryonic Kidney cells (HEK-293), and Allium cepa root apical meristem cells. Both squashed slide of the onion root tip and flow cytometric analysis of radish protoplast revealed a significantly increased frequency of polyploid cells. Flow cytometric analysis showed an increase in frequencies of G2-M in MCF-7 cells from 6.10 to 16.25% after clerodin (200μg/mL) treatment for 24 h. Confocal microscopy imaging of tubulin in clerodin-treated MCF-7 cells revealed microtubule destabilization. Molecular docking and LIGPLOT analysis indicate that clerodin interact in the colchicine binding site, including, single hydrog...
Mutagenesis, 2021
Potentilla fulgens is a medicinal plant in North-East India whose root is reported to have anti-d... more Potentilla fulgens is a medicinal plant in North-East India whose root is reported to have anti-diabetic, anticarcinogenic and antioxidant properties. The potential of hydro-alcoholic extract of P. fulgens root (PRE) for providing protection to mammalian cells exposed to ionising radiation was investigated in this study. The methanolic extract of PRE shows an enhanced radical scavenging ability in a concentration dependent manner. PRE-pre-treatment to stimulated human blood lymphocytes (HBLs) reduced the frequency of deletion and exchange aberrations induced by X-irradiation. Similar protection of chromosome aberrations was also observed in mouse bone marrow cells (BMCs) where mice were given PRE extract (1 mg extract/day/mice) ad libitum in the drinking water for 45 days before whole-body X-irradiation. Of the various extracts prepared by partitioning of the methanol extract, the ethyl-acetate (EA) fraction was found to possess better antioxidant, radical scavenging and DNA-damage ...
Scientific Reports, 2019
People of north-eastern states of India consume raw areca-nut (RAN) and lime which could lead to ... more People of north-eastern states of India consume raw areca-nut (RAN) and lime which could lead to oral, esophageal and gastric cancers. However, the incidence of these cancers are significantly lesser in those who consume pieces of Potentilla fulgens root along with RAN. Since evaluation of anticancer role, if any, of P. fulgens on RAN-mediated genetic alterations in human is difficult because of other compounding factors, this study was undertaken in mice to focus on gastric carcinogenesis since ad libitum administration of RAN extract with lime in drinking water induced stomach cancer due to greater exposure of its lining. A total of 160 mice were used at different time points and either methanol extract of P. fulgens roots (PRE) or mixture of four compounds of ethyl-acetate fraction (EA-mixture) was mixed with mice feed. Histological studies revealed that RAN + lime induced cancer in all the mice and interestingly only 20% developed cancer when PRE/EA-mixture was provided along wi...
Journal of Cellular Biochemistry, 2019
15-Lipoxygenase (15-LOX) belongs to the family of nonheme iron containing enzymes that catalyzes ... more 15-Lipoxygenase (15-LOX) belongs to the family of nonheme iron containing enzymes that catalyzes the peroxidation of polyunsaturated fatty acids (PUFAs) to generate eicosanoids that play an important role in signaling pathways. The role of 15-LOX has been demonstrated in atherosclerosis as well as other inflammatory diseases. In the present study, drug-like compounds were first screened from a set of anti-inflammatory phytochemicals based on Lipinski's rule of five (ROF) and in silico toxicity filters. Two lead compounds-quinine (QUIN) and rutaecarpine (RUT) were shortlisted by analyzing molecular interactions and binding energies of the filtered compounds with the target using molecular docking. Molecular dynamics simulation studies indicate stable trajectories of apo_15-LOX and docked complexes (15-LOX_QUIN and 15-LOX_RUT). In vitro 15-LOX inhibition studies shows that both QUIN and RUT have lower inhibitory concentration (IC 50) value than the control (quercetin). Both QUIN and RUT exhibit moderate antioxidant activities. The cell viability study of these compounds suggests no significant toxicity in HEK-293 cell lines. Further, QUIN and RUT both did not show any inhibition against selected Gram-positive and Gram-negative bacterial species. Thus, based on our present findings, rutaecarpine and quinine may be suggested as promising 15-LOX inhibitor for the prevention of the atherosclerosis development. K E Y W O R D S 15-lipoxygenase, anti-inflammatory phytochemicals, atherosclerosis, quinine, rutaecarpine 1 | INTRODUCTION Cardiovascular diseases (CVDs) are a set of diseases of the heart and blood vessels which include peripheral arterial disease, cerebrovascular disease, coronary, rheumatic heart disease, congenital heart disease, deep vein thrombosis, and pulmonary embolism. CVDs are the major cause of death in the world today. Around 17.7 million deaths were reported due to CVDs in 2015
Phytomedicine, 2019
Secondary metabolite profiling, cytotoxicity, anti-inflammatory potential and in vitro inhibitory... more Secondary metabolite profiling, cytotoxicity, anti-inflammatory potential and in vitro inhibitory activities of Nardostachys jatamansi on key enzymes linked to hyperglycemia, hypertension and cognitive disorders
International Journal of Phytomedicine, 2017
Streptococci and Lactobacilli are the most common bacteria causing dental caries. Potentilla fugl... more Streptococci and Lactobacilli are the most common bacteria causing dental caries. Potentilla fuglens, native of north-east India is used by tribal people to cure teeth and gum problems. Based on its ethomedical use, its anticariogenic potential was evaluated. The crude methanol extract was found to have good anticariogenic potential. Epigallocatechingallate (4) was found to the most effective inhibitor against the tested bacterial strains. Epiafzelechin (4β→8) epicatechin (8) also demonstrated comparatively better activity than other dimeric compounds (MIC of 1.56, 3.12 and 3.12 μg/mL against Streptococcus mutans, Lactobacillus acidophilus and Lactobacillus rhamnosus, respectively). Time-kill studies and biofilm formation inhibition assays showed molecule 8 to be comparable to compound 4 in terms of antibacterial action. The results suggest that these compounds and Potentilla extracts could be employed as natural antibacterial agents in oral health care products.
Scientific Reports, 2020
The Glutathione S-transferases (GSTs) protects cellular DNA against oxidative damage. The role of... more The Glutathione S-transferases (GSTs) protects cellular DNA against oxidative damage. The role of GSTP1 polymorphism (A313G; Ile105Val) as a susceptibility factor in oral cancer was evaluated in a hospital-based case-control study in North-East India, because the habit of chewing raw areca-nut (RAN) with/without tobacco is common in this region. Genetic polymorphism was investigated by genotyping 445 cases and 444 controls. Individuals with the GSTP1 AA-genotype showed association with the oral cancer (OR = 3.1, 95% CI = 2.4–4.2, p = 0.0002). Even after adjusting for age, sex and habit the AA-genotype is found to be significantly associated with oral cancer (OR = 2.4, 95% CI = 1.7–3.2, p = 0.0001). A protein-protein docking analysis demonstrated that in the GG-genotype the binding geometry between c-Jun Kinase and GSTP1 was disrupted. It was validated by immunohistochemistry in human samples, showing lower c-Jun-phosphorylation and down-regulation of pro-apoptotic genes in normal or...
Background Raw areca-nut (RAN) consumption induces oral, esophageal and gastric cancers which are... more Background Raw areca-nut (RAN) consumption induces oral, esophageal and gastric cancers which are significantly associated with the overexpression of pituitary tumor transforming gene1/Securin and chromosomal instability (CIN). Since the molecular mechanism underlying Securin upregulation remains unclear, this study is intended to investigate the association of Securin upregulation with Rb-E2F1 circuit and epigenetic histone (H3) modifications pattern both globally and in the promoter region of Securin gene. Methods Six groups of mice were used and in the treated group each mouse consumed 1 mg of RAN-extract with lime per day ad libitum in the drinking water for 60 days after which the dose was increased by 1 mg after every 60 days. Histopathological evaluation of stomach tissues was done and Securin expression was analysed by immunoblotting as well as by immunohistochemistry. ChIP-qPCR assay was performed for evaluating the recruitment of different histone modifications in the two ...
Cancer letters, Jan 27, 2018
Glutathione S-transferases (GSTs) are phase II detoxifying enzymes involved in the maintenance of... more Glutathione S-transferases (GSTs) are phase II detoxifying enzymes involved in the maintenance of cell integrity, oxidative stress and protection against DNA damage by catalyzing the conjugation of glutathione to a wide variety of electrophilic substrates. Though enzymes of the glutathione synthesis and salvage pathways have been well characterized in the past, there is still a lack of comprehensive understanding of their independent and coordinate regulatory mechanisms in carcinogenesis. The present review discusses implication of GST in cancer development and progression, gene polymorphism, drug resistance, signaling and epigenetic regulation involving their role in cancer. It is anticipated that GST especially the GSTP1 class can be developed as a biomarker either used alone or in combination with other biomarkers for early cancer detection and/or diagnosis as well as for future targeted preventive and therapeutic interventions with dietary agents.
International journal of biological macromolecules, 2018
An N-terminal truncated fibrino(geno)lytic serine protease gene encoding a ~42kDa protein from Ba... more An N-terminal truncated fibrino(geno)lytic serine protease gene encoding a ~42kDa protein from Bacillus cereus strain AB01 was produced by error prone PCR, cloned into pET19b vector, and expressed in E5 coli BL21 DE3 cells. The deletion of 24 amino acid residues from N-terminal of wild-type Bacifrinase improves the catalytic activity of [Bacifrinase (ΔN24)]. The anticoagulant potency of [Bacifrinase (ΔN24)] was comparable to Nattokinase and Warfarin and results showed that its anticoagulant action is contributed by progressive defibrinogenation and antiplatelet activities. Nonetheless, at the tested concentration of 2.0μM [Bacifrinase (ΔN24)] did not show in vitro cytotoxicity or chromosomal aberrations on human embryonic kidney cells-293 (HEK-293) and human peripheral blood lymphocytes (HPBL) cells. [Bacifrinase (ΔN24)], at a dose of 2mg/kg, did not show toxicity, adverse pharmacological effects, tissue necrosis or hemorrhagic effect after 72h of its administration in Swiss albino ...
Mutation Research Letters
ABSTRACT
Mutation research, Jan 9, 2016
Radiation induced DNA double-strand breaks (DSB) are the major initial lesions whose misrejoining... more Radiation induced DNA double-strand breaks (DSB) are the major initial lesions whose misrejoining may lead to exchange aberrations. However, the role of glutathione (GSH), a major cellular thiol, in regulating cell's sensitivity to DNA damaging agents is not well understood. Influence of endogenous GSH on the efficiency of X-rays and bleomycin (Blem) induced DNA DSBs end-joining has been tested here cytogenetically, in human lymphocytes and Hct116 cells. In another approach, oligomeric DNA (75bp) containing 5'-compatible and non-compatible overhangs mimicking the endogenous DSB were for rejoining in presence of cell-free extracts from cells having different endogenous GSH levels. Frequency of aberrations, particularly exchange aberrations, was significantly increased when Blem was combined with radiation. The exchange aberration frequency was further enhanced when combined treatment was given at 4°C since DNA lesions are poorly repaired at 4°C so that a higher number of DNA ...
Chemico-Biological Interactions, 2016
Ruviprase, a 4.4 kDa peptide isolated from Daboia russelii russelii venom demonstrated antiprolif... more Ruviprase, a 4.4 kDa peptide isolated from Daboia russelii russelii venom demonstrated antiproliferative activity against EMT6/AR1, U-87MG, HeLa and MCF-7 cancer cells with an IC50 value of 23.0, 8.8, 5.8 and 4.0 μg ml(-1), respectively. However, it was nontoxic to non-cancerous human embryonic kidney cell and human peripheral blood lymphocytes. Flow-cytometric analysis confirmed the apoptosis induction in MCF-7 cells by Ruviprase where it induced DNA condensation but did not cause mitotic blockage or chromosomal aberration in treated-cells. Immunofluorescence microscopic analysis indicated Ruviprase induced apoptosis in MCF-7 cells through p53 and p21-mediated pathways. Ruviprase generated reactive oxygen species (ROS), altered the mitochondrial transmembrane potential, and significantly decreased the cellular glutathione (GSH) content of MCF-7 cells. Immunoblotting and quantitative real-time PCR (qRT-PCR) analyses suggested that Ruviprase down-regulated the expression of anti-apoptotic protein Bcl-2, increased cleavage of poly (ADP-ribose) polymerase (PARP) protein, and up-regulated the expression of pro-apoptotic protein Bax, as well as executer protein caspase-7 to induced apoptosis in MCF-7 cells via intrinsic pathway. This is the first report on the characterization of the anticancer potential of a small, non-toxic and anticoagulant peptide purified from Russell's viper venom.
Cancer Research, Mar 3, 2001
Allelic deletions on the short arm of chromosome 6 (6p) are one of the common, possibly early, ge... more Allelic deletions on the short arm of chromosome 6 (6p) are one of the common, possibly early, genetic changes that occur in the pathogenesis of cervical carcinoma (CC). Previous loss of heterozygosity (LOH) studies in CC identified a number of critical regions of deletions on 6p. However, the precise location of minimally deleted regions and their role in precancerous lesions have not been well characterized. To address these questions, we first performed a detailed LOH analysis on 6p in 59 cases of invasive CC. The pattern of LOH identified two minimal regions of deletions, one spanning a 5 cM genetic distance at 6p25 and a second site of 10.3 cM deletion mapping to 6p21.3. The 6p21.3 minimal deletion spans HLA class I genes. To understand the role of 6p genetic alterations in the development of CC, we also investigated 12 high-grade and 4 low-grade cases of cervical intraepithelial neoplasia (CIN) for LOH after laser microdissection. The high-grade CINs exhibited 91.7% LOH, and low-grade CINs had 50% LOH. These findings implicate the presence of at least two tumor suppressor genes on 6p relevant to CC and suggest that these genetic alterations occur very early in CC development. This study should therefore facilitate the identification of tumor suppressor genes on 6p and may identify which CINs are at high risk of progressing to invasive CC.
New Biotechnology, 2010
ABSTRACT Food-borne fluke infections/trematodiases are emerging as a major public health problem ... more ABSTRACT Food-borne fluke infections/trematodiases are emerging as a major public health problem worldwide with over 40 million people affected and over 10% of world population at risk of infection. The major concentration of these infections is in Southeast Asian and Western Pacific Regions, where the epidemiological factors (including the prevalent socio-cultural food habits) are conducive for transmission of these infections. The preponderance of these infections is usually in food deficit poor communities that lack access to proper sanitary infrastructure. While targeting health for all, especially the poor rural tribal communities, it is imperative to take these infections into account. Bayesian analysis phylogeny of food-borne trematode parasites under study showed that they are closely related phylogenetic groups. To focus the control strategies at the target populations, the aim of the present study was to establish molecular methods for accurate discrimination between common food-borne trematodes parasites Paragonimus (lung fluke), Fasciolopsis (giant intestinal fluke) and Fasciola (liver fluke), the infections of which commonly prevail in NE India. In the first step, we amplified and sequenced the second internal transcribed spacer (ITS2) region of ribosomal DNA, utilizing nucleotide differences between the multiple sequence alignments of the parasites under study. Based upon the differences in nucleotide sequences of conserved regions, we designed species-specific primers that can unequivocally discriminate one species from another. ITS2 sequence motifs allowed an accurate in-silico distinction of the trematodes. The data indicate that ITS2 motifs (≤ 50 bp in size) can be considered promising tool for trematode species identification. Using molecular morphometrics that is based on ITS2 secondary structure homologies, phylogenetic relationships with various isolates of several trematode species have been discussed. The present results suggest that the ITS2 specific primers can be used for epidemiological investigations of the prevalence of trematodiasis.
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Papers by Anupam Chatterjee