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1.
Vet Parasitol Reg Stud Reports ; 52: 101056, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38880573

ABSTRACT

This study focuses on the occurrence, identification, and molecular characterization of Eimeria species causing coccidiosis in cattle in the Kashmir Valley, India. Coccidiosis, caused by apicomplexan parasites of the genus Eimeria, poses a significant threat to global cattle farming. Conventional techniques for identification, which rely on the morphology of sporulated oocysts, have drawbacks, leading to the adoption of molecular techniques to accurately delimit species. A total of 190 cattle were sampled in nine farms and parasitological examination revealed an occurrence of 45.7% for Eimeria spp. Molecular analysis using PCR and sequencing identified three predominant species: E. zuernii, E. alabamensis, and E. bovis. The study highlights the widespread occurrence of these species globally, as supported by previous research conducted in Bangladesh, Austria, Egypt, and Brazil. The phylogenetic analysis based on internal transcribed spacer (ITS-1) gene sequences revealed distinct clusters for E. zuernii and E. bovis, while E. alabamensis formed a separate clade. The genetic diversity and phylogenetic connections provide insights into the evolutionary relationships among these Eimeria species. This study contributes valuable information for understanding the epidemiology and genetic diversity of cattle coccidiosis in the Kashmir Valley, emphasizing the importance of molecular characterization for accurate species identification.


Subject(s)
Cattle Diseases , Coccidiosis , Eimeria , Genetic Variation , Animals , Cattle , Coccidiosis/epidemiology , Coccidiosis/parasitology , Coccidiosis/veterinary , Eimeria/classification , Eimeria/genetics , Cattle Diseases/epidemiology , Cattle Diseases/parasitology , India/epidemiology , Phylogeny , Polymerase Chain Reaction , DNA, Ribosomal Spacer/genetics
2.
Res Vet Sci ; 164: 105001, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37690328

ABSTRACT

Development of anticoccidial resistance and concerns of drug residues have prompted the evaluation of alternatives to allopathic drugs. In current study, anticoccidial effect of amprolium was compared with that of Curcuma longa and Zingiber officinale. Ninety (90) sheep, naturally infected with Eimeria spp. and having a minimum oocyst per gram (OPG) count of faeces above 5000 were randomly selected and divided into six groups of 15 animals each. Animals were supplemented with amprolium @ 62.50 mg/kg body weight (bw) (GI), turmeric @ 200 and 300 mg/kg bw (GII and GIII) and ginger @ 200 and 300 mg/kg bw (GIV and GV), orally for 7 days and GVI animals were kept as untreated infected control. Faecal samples were collected on '0' day before treatment and on 8th, 14th, 21st and 28th day after starting treatment and evaluated using Faecal oocyst count reduction test (FOCRT). The efficacy of amprolium was 93.18%, 96.82%, 95.56% and 95.80% on 8th, 14th, 21st and 28th day, after starting treatment. Turmeric @200 mg/kg b.w. showed efficacy of 41.49%, 52.37%, 61.47% and 60.08% and turmeric @ 300 mg/kg bw was 44.92%, 54.32%, 64.21% and 61.95% effective on 8th, 14th, 21st and 28th day, respectively. Ginger @200 mg/kg bw showed efficacy of 38.51%, 53.48%, 55.38% and 55.53% and ginger @ 300 mg/kg bw was 39.65%, 54.81%, 57.18% and 58.22% effective on 8th,14th, 21st and 28th day, respectively. The results justify use of amprolium for clinical coccidiosis while Curcuma longa and Gingiber officinale could be used as natural prophylactic alternatives.


Subject(s)
Coccidiosis , Eimeria , Sheep Diseases , Animals , Sheep , Amprolium/pharmacology , Amprolium/therapeutic use , Coccidiosis/drug therapy , Coccidiosis/veterinary , Feces , Oocysts , Sheep Diseases/drug therapy
3.
Crit Rev Oncol Hematol ; 183: 103915, 2023 Mar.
Article in English | MEDLINE | ID: mdl-36702424

ABSTRACT

In breast cancer, mAbs can play multifunctional roles like targeting cancer cells, sometimes directly attacking them, helping in locating and delivering therapeutic drugs to targets, inhibiting cell growth and blocking immune system inhibitors, etc. Monoclonal antibodies are also one of the important successful treatment strategies especially against HER2 but they have not been explored much for other types of breast cancers especially in triple negative breast cancers. Monoclonal antibodies impact the feasibility of antigen specificity, bispecific and trispecific mAbs have opened new doors for more targeted specific efficacy. Monoclonal antibodies can be used diversly and with efficacy as compared to other methods of treatment thus maining it a suitable candidate for breast cancer treatment. However, mAbs treatment also causes various side effects such as fever, trembling, fatigue, headache and muscle pain, nausea/vomiting, difficulty in breathing, rashes and bleeding. Understanding the pros and cons of this strategy, we have explored in this review, the current and future potential capabilities of monoclonal antibodies with respect to diagnosis and treatment of breast cancer. DATA AVAILABILITY: Not applicable.


Subject(s)
Breast Neoplasms , Triple Negative Breast Neoplasms , Humans , Female , Antibodies, Monoclonal/therapeutic use , Breast Neoplasms/drug therapy , Triple Negative Breast Neoplasms/drug therapy , Cell Proliferation
4.
Int J Biol Macromol ; 205: 154-168, 2022 Apr 30.
Article in English | MEDLINE | ID: mdl-35181322

ABSTRACT

P66Shc is the master regulator of oxidative stress whose pro-oxidant functioning is governed by ser36 phosphorylation. Phosphorylated p66Shc via Rac1 GTPase activation modulates ROS levels which in turn influence its pro-oxidative functions. Vitamin C at higher concentrations exhibits cytotoxic activity in various cancers, inducing ROS mediated cell death via pro-apoptotic mechanisms. Here we show a novel role of p66Shc in mediating pro-oxidant activity of vitamin C. Effect of vitamin C on the viability of breast cancer and normal cells was studied. High doses of vitamin C decreased viability of cancerous cells but not normal cells. Docking study displayed significant binding affinity of vitamin C with p66Shc PTB domain. Western blot results suggest that vitamin C not only enhances p66Shc expression but also induces its ser36 phosphorylation. Vitamin C at high doses was also found to activate Rac1, enhance ROS production and induce apoptosis. Interestingly, ser36 phosphorylation mutant transfection and pretreatment with antioxidant N-acetylcysteine results indicate that vitamin C induced Rac1 activation, ROS production and apoptosis is p66Shc ser36 phosphorylation dependent. Overall, results highlight that vitamin C mechanistically explores p66Shc/Rac1 pathway in inducing apoptosis and thus can pave a way to use this pathway as a potential therapeutic target in breast cancers.


Subject(s)
Ascorbic Acid , Oxidative Stress , Ascorbic Acid/pharmacology , Phosphorylation , Reactive Oxygen Species/metabolism , Shc Signaling Adaptor Proteins/genetics , Shc Signaling Adaptor Proteins/metabolism , Src Homology 2 Domain-Containing, Transforming Protein 1/genetics , Src Homology 2 Domain-Containing, Transforming Protein 1/metabolism , Src Homology 2 Domain-Containing, Transforming Protein 1/pharmacology , rac1 GTP-Binding Protein/metabolism
5.
Phytother Res ; 35(7): 3861-3874, 2021 Jul.
Article in English | MEDLINE | ID: mdl-33826182

ABSTRACT

Geraniol, an acyclic monoterpene present in several plant species' essential oils, is utilized as a food additive. It possesses potent antiproliferative and antitumor effects ascribed to its antiinflammatory, and antioxidant properties. The study aimed to understand geraniol's mechanism in human lung and skin cancer cells by employing molecular and cell target-based assays. SRB, NRU, MTT assays, qRT-PCR, molecular docking, and EAC model were used. Geraniol inhibits the proliferation of PC-3, A431, and A549 cells (~50%) and suppresses the activity of ornithine decarboxylase (15.42 ± 0.61 µM) and hyaluronidase (57.61 ± 8.53 µM) in A549 cells; LOX-5 (25.44 ± 3.50 µM) and hyaluronidase (90.71 ± 2.38 µM) in A431 cells. The qRT-expression analysis of the targeted gene depicts non-significant change at the transcriptional level of LOX-5 in A431 cells. A robust binding interaction of geraniol with molecular targets was observed in the molecular docking studies. In Ehrlich Ascites Carcinoma model, geraniol inhibit tumor growth by 50.08% at 75 mg/kg bw and was found to be safe up to 1,000 mg/kg bw in a toxicity study. Geraniol has two prenyl units allied head-to-tail and functionalized with one hydroxyl group at its tail end could be responsible for the antiproliferative activity. These observations provide evidence for geraniol to be used as a new prototype to develop a novel anticancer agent.


Subject(s)
Acyclic Monoterpenes/pharmacology , Carcinoma , Lung Neoplasms/drug therapy , Skin Neoplasms , A549 Cells , Carcinoma/drug therapy , Cell Line, Tumor , Humans , Molecular Docking Simulation , Skin Neoplasms/drug therapy
6.
J Adv Res ; 34: 93-107, 2021 12.
Article in English | MEDLINE | ID: mdl-35024183

ABSTRACT

Introduction: Neomenthol, a cyclic monoterpenoid, is a stereoisomer of menthol present in the essential oil of Mentha spp. It is used in food as a flavoring agent, in cosmetics and medicines because of its cooling effects. However, neomenthol has not been much explored for its anticancer potential. Additionally, targeting hyaluronidase, Cathepsin-D, and ODC by phytochemicals is amongst the efficient approach for cancer prevention and/or treatment. Objectives: To investigate the molecular and cell target-based antiproliferative potential of neomenthol on human cancer (A431, PC-3, K562, A549, FaDu, MDA-MB-231, COLO-205, MCF-7, and WRL-68) and normal (HEK-293) cell lines. Methods: The potency of neomenthol was evaluated on human cancer and normal cell line using SRB, NRU and MTT assays. The molecular target based study of neomenthol was carried out in cell-free and cell-based test systems. Further, the potency of neomenthol was confirmed by quantitative real-time PCR analysis and molecular docking studies. The in vivo anticancer potential of neomenthol was performed on mice EAC model and the toxicity examination was accomplished through in silico, ex vivo and in vivo approaches. Results: Neomenthol exhibits a promising activity (IC50 17.3 ± 6.49 µM) against human epidermoid carcinoma (A431) cells by arresting the G2/M phase and increasing the number of sub-diploid cells. It significantly inhibits hyaluronidase activity (IC50 12.81 ± 0.01 µM) and affects the tubulin polymerization. The expression analysis and molecular docking studies support the in vitro molecular and cell target based results. Neomenthol prevents EAC tumor formation by 58.84% and inhibits hyaluronidase activity up to 10% at 75 mg/kg bw, i.p. dose. The oral dose of 1000 mg/kg bw was found safe in acute oral toxicity studies. Conclusion: Neomenthol delayed the growth of skin carcinoma cells by inhibiting the tubulin polymerization and hyaluronidase activity, which are responsible for tumor growth, metastasis, and angiogenesis.


Subject(s)
Skin Neoplasms , Tubulin , Animals , Cell Proliferation , HEK293 Cells , Humans , Hyaluronoglucosaminidase , Mice , Molecular Docking Simulation , Polymerization , Skin Neoplasms/drug therapy
7.
J Gene Med ; 22(11): e3260, 2020 11.
Article in English | MEDLINE | ID: mdl-32783258

ABSTRACT

BACKGROUND: Germline genetic variants of human telomerase reverse transcriptase (hTERT) are known to predispose for various malignancies, including glioma. The present study investigated genetic variation of hTERT T/G (rs2736100) and hTERT G/A (rs2736098) with respect to glioma risk. METHODS: Confirmed cases (n = 106) were tested against 210 cancer-free healthy controls by the polymerase chain reaction-restriction fragment length polymorphism technique for genotyping. RESULTS: Homozygous variant 'GG' genotype of rs2736100 frequency was > 4-fold significantly different in cases versus controls (39.6% 17.2%; p < 0.0001). Furthermore, variant 'G' allele was found to be significantly associated with cases (0.5 versus 0.2 in controls; p < 0.0001). Homozygous variant rs2736098 'AA' genotype (35.8% versus 23.8%) and allele 'A' (0.49 versus 0.34) showed a marked significant difference in cases and controls, respectively (p < 0.05). In hTERT rs2736100, the GG genotype significantly presented more in higher grades and GBM (p < 0.0001). Furthermore, the GG variant of hTERT rs2736100 had a poor probability with respect to the overall survival of patients compared to TG and TT genotypes (log rank p = 0.03). Interestingly, two haplotypes of hTERT rs2736100/rs2736098 were identified as GG and GA that conferred a > 3- and 5-fold risk to glioma patients respectively, where variant G/A haplotype was observed to have the highest impact with respect to glioma risk (p < 0.0001). CONCLUSIONS: The results of the present study indicate that hTERT rs2736098 and rs2736100 variants play an important role in conferring a strong risk of developing glioma. Furthermore, hTERT rs2736100 GG variant appears to play a role in the bad prognosis of glioma patients. Haplotypes GG and GA could prove to be vital tools for monitoring risk in glioma patients.


Subject(s)
Biomarkers, Tumor/genetics , Gene Expression Regulation, Neoplastic , Genetic Predisposition to Disease , Glioma/mortality , Glioma/pathology , Polymorphism, Single Nucleotide , Telomerase/genetics , Adult , Case-Control Studies , Female , Genotype , Glioma/classification , Glioma/genetics , Humans , Male , Prognosis , Survival Rate
8.
Bioorg Med Chem Lett ; 30(11): 127138, 2020 06 01.
Article in English | MEDLINE | ID: mdl-32247734

ABSTRACT

A series of amide derivatives of stilbene was synthesized and investigated for osteogenic activity. Out of sixteen, seven compounds viz19c, 19g, 19i, 24b, 25a, 25c and 26a showed significant osteoblast differentiation within 1 pM-1 µM concentrations. Amongst all, 26a was identified as most active molecule which presented effective mineralization of osteoblasts and expression of mRNA of osteogenic marker gene such as BMP-2, ALP, and Runx-2 at 1 pM. In estrogen-deficient balb/c mice, 26a showed significant osteogenic activity at 5 mg-kg-1 body weight dose. The protein expression study for estrogen receptors α and ß (ER-α & ER-ß) using mouse calvarial osteoblasts (MCOs) and molecular docking analyses showed preferential expression of ER-ß by 26a indicating the possibility of ER-ß mediated osteogenic activity of 26a.


Subject(s)
Amides/chemistry , Stilbenes/chemistry , Animals , Binding Sites , Bone Morphogenetic Protein 2/genetics , Bone Morphogenetic Protein 2/metabolism , Cell Differentiation/drug effects , Cell Survival/drug effects , Core Binding Factor Alpha 1 Subunit/genetics , Core Binding Factor Alpha 1 Subunit/metabolism , Estrogen Receptor alpha/genetics , Estrogen Receptor alpha/metabolism , Estrogen Receptor beta/chemistry , Estrogen Receptor beta/genetics , Estrogen Receptor beta/metabolism , Humans , MCF-7 Cells , Mice , Mice, Inbred BALB C , Molecular Docking Simulation , Osteoblasts/cytology , Osteoblasts/metabolism , Osteogenesis/drug effects , RNA, Messenger/metabolism , Raloxifene Hydrochloride/chemistry , Raloxifene Hydrochloride/metabolism , Raloxifene Hydrochloride/pharmacology , Stilbenes/metabolism , Stilbenes/pharmacology
9.
Fungal Biol ; 123(5): 373-383, 2019 05.
Article in English | MEDLINE | ID: mdl-31053326

ABSTRACT

A total of 266 endophytic fungal isolates were recovered from 1019 tissue segments of Glycyrrhiza glabra collected from four different locations in the North-Western Himalayas. The endophytes grouped into 21 genera and 38 different taxa. The host had strong affinity for the genus Phoma, followed by Fusarium. The species richness was highest at the sub-tropical location, followed by the sub-temperate location and the temperate locations, respectively. The tissue specificity of endophytes was also evident. Some endophytes showed potential antimicrobial activity against phyto-pathogens indicating that they may be helpful to the host in evading pathogens. All the endophytic taxa produced the plant growth promoting hormone, indole acetic acid (IAA), though in varying concentrations. None of these endophytes caused any symptoms of disease in co-cultivation with the tissue cultured plants. Further, all the endophytes had a positive influence on the phenolic and flavonoid content of the host. Three endophytes, Stagonosporopsis cucurbitacearum, Bionectria sp. and Aspergillus terreus also increased the host root (rhizome) and shoot growth visibly. Such endophytes are potential candidates for developing endophyte-based technologies for sustainable cultivation and enhanced productivity of G. glabra. This is the first report of community structure and biological properties of fungal endophytes associated with G. glabra.


Subject(s)
Endophytes/classification , Endophytes/isolation & purification , Fungi/classification , Fungi/isolation & purification , Glycyrrhiza/microbiology , Symbiosis , Anti-Infective Agents/metabolism , Endophytes/genetics , Endophytes/physiology , Fungi/genetics , Fungi/physiology , India , Plant Development
10.
Curr Microbiol ; 75(7): 880-887, 2018 Jul.
Article in English | MEDLINE | ID: mdl-29492649

ABSTRACT

Saffron (Crocus sativus L.) is one of the most expensive spices in the world due to its medicinal and aromatic value. However, saffron production is severely affected by the corm rot disease throughout the saffron producing countries. In this study, we report a basidiomycetous latent pathogen of saffron, designated as CSE26, capable of producing phytotoxic compounds. CSE26 is a highly odorous basidiomycete with monomitic hyphal system. Molecular phylogeny of ITS and 28S ribosomal gene sequence of CSE26 assigned it as Porostereum spadiceum. It was found to produce corm rot in C. sativus under in vivo and field conditions, with a disease severity index of 0.7 and 0.5, respectively. CSE26 was found to produce chlorinated aromatic compounds (CAMs) having phytotoxic activity against Arabidopsis plants. Therefore, these compounds may be acting as pathogenic determinants of CSE26. However, there is a need to study the level of production of these CAMs by this fungus in the natural environment and their effects on plant health.


Subject(s)
Crocus/microbiology , Herbicides/metabolism , Hydrocarbons, Aromatic/metabolism , Hydrocarbons, Chlorinated/metabolism , Plant Diseases/microbiology , Polyporales/chemistry , Polyporales/isolation & purification , Arabidopsis/drug effects , Herbicides/pharmacology , Hydrocarbons, Aromatic/pharmacology , Hydrocarbons, Chlorinated/pharmacology , Phylogeny , Polyporales/genetics , Polyporales/metabolism
11.
Sci Rep ; 7(1): 8598, 2017 08 17.
Article in English | MEDLINE | ID: mdl-28819197

ABSTRACT

Crocus sativus is the only plant species which produces apocarotenoids like crocin, picrocrocin and safranal in significant amounts. These compounds impart organoleptic properties to saffron (dried stigmas of Crocus flower) making it world's costliest spice. Crocus apocarotenoids have tremendous medicinal properties as well. Effect of endophytes on Crocus apocarotenoid production and the molecular mechanism involved has not been reported so far. Here we studied the effect of an oleaginous fungal endophyte, Mortierella alpina CS10E4 on Crocus growth, apocarotenoid metabolism and tolerance to corm rot disease. The results demonstrated that there was a significant improvement in many morphological and physiological traits in endophyte treated Crocus plants including total biomass and size of corms, stigma biomass, number of apical sprouting buds, and number of adventitious roots. The endophyte also shifted metabolic flux towards enhanced production of apocarotenoids by modulating the expression of key pathway genes. Further, M. alpina CS10E4 enhanced tolerance to corm rot disease by releasing arachidonic acid which acts as conserved defense signal and induces jasmonic acid production in endophyte treated Crocus corms. This is first report on effect of a fungal endophyte on Crocus apocarotenoid metabolism and stress tolerance.


Subject(s)
Adaptation, Physiological , Carotenoids/biosynthesis , Crocus/microbiology , Crocus/physiology , Endophytes/physiology , Mortierella/physiology , Stress, Physiological , Adaptation, Physiological/genetics , Crocus/genetics , Crocus/growth & development , Cyclopentanes/metabolism , Endophytes/isolation & purification , Flavonoids/analysis , Gene Expression Regulation, Plant , Mortierella/isolation & purification , Oxylipins/metabolism , Phenols/analysis , Phylogeny , Plant Diseases/microbiology , Secondary Metabolism , Stress, Physiological/genetics
12.
Fungal Biol ; 120(12): 1509-1524, 2016 12.
Article in English | MEDLINE | ID: mdl-27890087

ABSTRACT

A total of 294 fungal endophytes were isolated from the corms of Crocus sativus at two stages of crocus life cycle collected from 14 different saffron growing sites in Jammu and Kashmir (J & K) State, India. Molecular phylogeny assigned them into 36 distinct internal transcribed spacer (ITS) genotypes which spread over 19 genera. The diversity of endophytes was higher at the dormant than at the vegetative stage. The Saffron microbiome was dominated by Phialophora mustea and Cadophora malorum, both are dark septate endophytes (DSEs). Some endophytes were found to possess antimicrobial properties that could be helpful for the host in evading the pathogens. These endophytes generally produced significant quantities of indole acetic acid (IAA) as well. However, thirteen of the endophytic taxa were found to cause corm rot in the host with different levels of severity under in vitro as well as in vivo conditions. This is the first report of community structure and biological properties of fungal endophytes associated with C. sativus, which may eventually help us to develop agro-technologies, based on plant-endophyte interactions for sustainable cultivation of saffron. The endophytes preserved ex situ, in this study, may also yield bioactive natural products for pharmacological and industrial applications.


Subject(s)
Crocus/microbiology , Endophytes/classification , Endophytes/genetics , Genetic Variation , Mycobiome , Plant Growth Regulators/metabolism , Anti-Bacterial Agents/metabolism , Cluster Analysis , DNA, Fungal/chemistry , DNA, Fungal/genetics , DNA, Ribosomal Spacer/chemistry , DNA, Ribosomal Spacer/genetics , Endophytes/metabolism , India , Indoleacetic Acids/metabolism , Phylogeny , Plant Diseases/microbiology , Sequence Analysis, DNA
13.
Microb Ecol ; 72(4): 802-812, 2016 11.
Article in English | MEDLINE | ID: mdl-27357141

ABSTRACT

During the screening of endophytes obtained from Glycyrrhiza glabra Linn., the extract from a fungal culture designated as GG1F1 showed significant antimicrobial activity. The fungus was identified as a species of the genus Phoma and was most closely related to Phoma cucurbitacearum. The chemical investigation of the GG1F1 extract led to the isolation and characterization of two thiodiketopiperazine derivatives. Both the compounds inhibited the growth of several bacterial pathogens especially that of Staphylococcus aureus and Streptococcus pyogenes, with IC50 values of less than 10 µM. The compounds strongly inhibited biofilm formation in both the pathogens. In vitro time kill kinetics showed efficient bactericidal activity of these compounds. The compounds were found to act synergistically with streptomycin while producing varying effects in combination with ciprofloxacin and ampicillin. The compounds inhibited bacterial transcription/translation in vitro, and also inhibited staphyloxanthin production in S. aureus. Although similar in structure, they differed significantly in some of their properties, particularly the effect on the expression of pathogenecity related genes in S. aureus at sub-lethal concentrations. Keeping in view the antimicrobial potential of these compounds, it would be needful to scale up the production of these compounds through fermentation technology and further explore their potential as antibiotics using in vivo models.


Subject(s)
Anti-Bacterial Agents/pharmacology , Endophytes/metabolism , Glycyrrhiza/microbiology , Saccharomycetales/metabolism , Staphylococcus aureus/growth & development , Streptococcus pyogenes/growth & development , Ampicillin/pharmacology , Anti-Bacterial Agents/isolation & purification , Anti-Bacterial Agents/metabolism , Biofilms/drug effects , Biofilms/growth & development , Ciprofloxacin/pharmacology , Drug Combinations , Microbial Sensitivity Tests , Real-Time Polymerase Chain Reaction , Streptomycin/pharmacology , Xanthophylls/biosynthesis
14.
Food Chem Toxicol ; 87: 1-11, 2016 Jan.
Article in English | MEDLINE | ID: mdl-26615871

ABSTRACT

We have synthesized a novel quinazolinone chalcone derivative (QC) and first time reported its in-vitro and in-vivo anticancer potential. It inhibited the cell proliferation of different cancer cell lines like PC-3, Panc-1, Mia-Paca-2, A549, MCF-7 and HCT-116. It induces apoptosis as measured by several biological endpoints such as apoptotic body formation, evident by Hoechst and scanning electron microscopy, enhanced annexinV-FITC binding of the cells, increased sub-G0 cell fraction, loss of mitochondrial membrane potential (Δψm), reduction of Bcl-2/Bax ratio, activation of caspase-9, caspase-3 and PARP-1 (poly-ADP Ribose polymerase) cleavage in HCT-116 cells. In spite of apoptosis, QC significantly hammers the downstream and upstream signaling cascade of PI3K/Akt/mTOR pathway and cell cycle regulator Skp-2, p21 and p27. Interestingly, QC induces the S and G2/M phase of HCT-116 cells at experimental doses. QC inhibits the tumor growth of Ehrlich ascites carcinoma (EAC), Ehrlich tumor (ET, solid) and sarcoma-180(solid) mice models. Furthermore, it was found to be non-toxic as no animal mortality (0/7) occurred during experimental doses. The present study provides an insight of anticancer potential of QC, which may be useful in managing and treating cancer.


Subject(s)
Apoptosis/drug effects , Chalcones/pharmacology , Phosphatidylinositol 3-Kinases/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Quinazolinones/pharmacology , TOR Serine-Threonine Kinases/metabolism , Animals , Cell Cycle/drug effects , Cell Line, Tumor , Cell Proliferation/drug effects , Chalcones/chemistry , Humans , Membrane Potential, Mitochondrial/drug effects , Mice , Molecular Structure , Neoplasms, Experimental/drug therapy , Phosphatidylinositol 3-Kinases/genetics , Proto-Oncogene Proteins c-akt/genetics , Quinazolinones/chemistry , Random Allocation , Signal Transduction/drug effects , TOR Serine-Threonine Kinases/genetics
15.
BMC Genomics ; 16: 698, 2015 Sep 15.
Article in English | MEDLINE | ID: mdl-26370545

ABSTRACT

BACKGROUND: Crocus sativus stigmas form rich source of apocarotenoids like crocin, picrocrocin and saffranal which besides imparting color, flavour and aroma to saffron spice also have tremendous pharmacological properties. Inspite of their importance, the biosynthetic pathway of Crocus apocarotenoids is not fully elucidated. Moreover, the mechanism of their stigma specific accumulation remains unknown. Therefore, deep transcriptome sequencing of Crocus stigma and rest of the flower tissue was done to identify the genes and transcriptional regulators involved in the biosynthesis of these compounds. RESULTS: Transcriptome of stigma and rest of the flower tissue was sequenced using Illumina Genome Analyzer IIx platform which generated 64,604,402 flower and 51,350,714 stigma reads. Sequences were assembled de novo using trinity resulting in 64,438 transcripts which were classified into 32,204 unigenes comprising of 9853 clusters and 22,351 singletons. A comprehensive functional annotation and gene ontology (GO) analysis was carried out. 58.5 % of the transcripts showed similarity to sequences present in public databases while rest could be specific to Crocus. 5789 transcripts showed similarity to transcription factors representing 76 families out of which Myb family was most abundant. Many genes involved in carotenoid/apocarotenoid pathway were identified for the first time in this study which includes zeta-carotene isomerase and desaturase, carotenoid isomerase and lycopene epsilon-cyclase. GO analysis showed that the predominant classes in biological process category include metabolic process followed by cellular process and primary metabolic process. KEGG mapping analysis indicated that pathways involved in ribosome, carbon and starch and sucrose metabolism were highly represented. Differential expression analysis indicated that key carotenoid/apocarotenoid pathway genes including phytoene synthase, phytoene desaturase and carotenoid cleavage dioxygenase 2 are enriched in stigma thereby providing molecular proof for stigma to be the site of apocarotenoid biosynthesis. CONCLUSIONS: This data would provide a rich source for understanding the carotenoid/apocarotenoid metabolism in Crocus. The database would also help in investigating many questions related to saffron biology including flower development.


Subject(s)
Carotenoids/biosynthesis , Crocus/genetics , Crocus/metabolism , Gene Expression Profiling , Gene Expression Regulation, Plant , Transcriptome , Cluster Analysis , Computational Biology/methods , High-Throughput Nucleotide Sequencing , Molecular Sequence Annotation , Phylogeny , Reproducibility of Results , Transcription Factors/genetics
16.
J Tradit Complement Med ; 5(1): 35-41, 2015 Jan.
Article in English | MEDLINE | ID: mdl-26151007

ABSTRACT

Cancer is a leading cause of death worldwide and sustained focus is on the discovery and development of newer and better tolerated anticancer drugs especially from plants. The sulforhodamine B (SRB) in vitro cytotoxicity assay, sarcoma-180 (S-180) ascites and solid tumor, and L1210 lymphoid leukemia in vivo models were used to investigate the anticancer activity of root extracts of Aristolochia ringens Vahl. (Aristolochiaceae; mǎ dou líng). AR-A001 (IC50 values of 20 µg/mL, 22 µg/mL, 3 µg/mL, and 24 µg/mL for A549, HCT-116, PC3, and THP-1 cell lines, respectively), and AR-A004 (IC50 values of 26 µg/mL, 19.5 µg/mL, 12 µg/mL, 28 µg/mL, 30 µg/mL, and 22 µg/mL for A549, HCT-116, PC3, A431, HeLa, and THP-1, respectively), were observed to be significantly active in vitro. Potency was highest with AR-A001 and AR-A004 for PC3 with IC50 values of 3 µg/mL and 12 µg/mL, respectively. AR-A001 and AR-A004 produced significant (p < 0.05-0.001) dose-dependent inhibition of tumor growth in the S-180 ascites model with peak effects produced at the highest dose of 120 mg/kg. Inhibition values were 79.51% and 89.98% for AR-A001 and AR-A004, respectively. In the S-180 solid tumor model, the inhibition of tumor growth was 29.45% and 50.50% for AR-A001 (120 mg/kg) and AR-A004 (110 mg/kg), respectively, compared to 50.18% for 5-fluorouracil (5-FU; 20 mg/kg). AR-A001 and AR-A004 were also significantly active in the leukemia model with 211.11% and 155.56% increase in mean survival time (MST) compared to a value of 211.11% for 5-FU. In conclusion, the ethanolic (AR-A001) and dichloromethane:methanol (AR-A004) root extracts of AR possess significant anticancer activities in vitro and in vivo.

17.
Org Biomol Chem ; 13(20): 5674-89, 2015 May 28.
Article in English | MEDLINE | ID: mdl-25895604

ABSTRACT

Colchicine (1), a nature-derived microtubule polymerization inhibitor, develops multi-drug resistance in tumor cells due to its P-gp substrate and induction activity, which in turn leads to its rapid efflux from tumor cells. This auto-induction of the efflux of colchicine remains a major challenge to medicinal chemists. Based on structure-based molecular modeling, a series of new colchicine derivatives were designed and synthesized with a potential for reduced P-gp induction liability. Screening of the prepared derivatives for P-gp induction activity revealed that a number of derivatives possess remarkably lower P-gp-induction activity (>90% intracellular accumulation of rhodamine 123 in LS-180 cells) compared to the parent natural product colchicine (62% Rh123 accumulation in LS-180 cells). The reduced P-gp-induction activity of new derivatives may be due to their reduced ability to interact and change the conformation of P-gp. The synthesized derivatives were then screened for antiproliferative activity against two colon cancer cell lines including HCT-116 and Colo-205. The derivative 4o showed potent cytotoxicity in HCT-116 cells with IC50 of 0.04 µM with significantly reduced P-gp induction liability. Compound 4o also inhibited microtubule assembly and induced expression of pro-apoptotic protein p21. In an Ehrlich solid tumor mice model, compound 4o showed 38% TGI with no mortality at 2 mg kg(-1) dose (oral). Compound 4o, with potent in vitro and in vivo anticancer activity, significantly reduced P-gp induction activity and its excellent physicochemical and pharmacokinetic properties open up new opportunities for the colchicine scaffold.


Subject(s)
ATP Binding Cassette Transporter, Subfamily B/metabolism , Acetamides/pharmacology , Antineoplastic Agents/pharmacology , Carcinoma, Ehrlich Tumor/pathology , Cell Proliferation/drug effects , Colchicine/analogs & derivatives , Colchicine/pharmacology , Colonic Neoplasms/pathology , Tubulin Modulators/pharmacology , ATP Binding Cassette Transporter, Subfamily B/chemistry , Acetamides/chemistry , Acetamides/pharmacokinetics , Animals , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacokinetics , Blotting, Western , Carcinoma, Ehrlich Tumor/drug therapy , Colchicine/chemistry , Colchicine/pharmacokinetics , Colonic Neoplasms/drug therapy , Gene Expression Regulation, Neoplastic/drug effects , Humans , Male , Mice , Protein Conformation , Tissue Distribution , Tubulin Modulators/chemistry , Tumor Cells, Cultured
18.
Article in English | MEDLINE | ID: mdl-25810744

ABSTRACT

Introduction. Sansevieria liberica Gerome and Labroy (Agavaceae) is a perennial plant widely distributed in tropical Africa. Preparations of the plant are commonly used across Nigeria for the treatment of inflammatory conditions. Based on the fact that herbal medicine is a strong component of integrative medicine, this study was conducted to evaluate the anticancer activity of root extracts of Sansevieria liberica. Methods. Sulforhodamine B (SRB) in vitro cytotoxicity assay, Sarcoma-180 (S-180) ascites and solid tumor, and L1210 lymphoid leukemia in vivo models were used in this study. Results. SL-A002 (IC50 23 µg/mL with HeLa), SL-A003 (IC50 22 µg/mL with HCT-116), and SL-A004 (IC50 23 and 18 µg/mL with A549 and THP-1, resp.) demonstrated significant activity in the SRB cytotoxicity assay. Potency was highest with the following pairs of extract : cancer cell line: SL-A002 : HeLa (IC50 23 µg/mL), SL-A003 : HCT-116 (IC50 22 µg/mL), and SL-A004 : THP-1 (IC50 18 µg/mL). SL-A002 demonstrated significant dose-dependent antitumor activity in the Sarcoma-180 (S-180) ascites model with peak effect produced at the dose of 120 mg/kg (i.p.) with inhibition of 89.36% compared to 97.96% for 5-FU (20 mg/kg i.p.). The inhibition of tumor growth by SL-A002 in the S-180 solid tumor model was 47.40% compared to a value of 50.18% for 5-FU. SL-A002 was also significantly active in the L1210 lymphoid leukemia model with 158.33% increase in mean survival time, the same value for 5-FU. Conclusions. The hydroethanolic extract of Sansevieria liberica, SL-A002, possesses significant anticancer activity to warrant further extensive study to identify, isolate, and characterize the specific bioactive molecules responsible for the observed antitumor activity and the precise mechanism(s) of action.

19.
Appl Microbiol Biotechnol ; 99(7): 2955-65, 2015 Apr.
Article in English | MEDLINE | ID: mdl-25750045

ABSTRACT

Endophytism is the phenomenon of mutualistic association of a plant with a microorganism wherein the microbe lives within the tissues of the plant without causing any symptoms of disease. In addition to being a treasured biological resource, endophytes play diverse indispensable functions in nature for plant growth, development, stress tolerance, and adaptation. Our understanding of endophytism and its ecological aspects are overtly limited, and we have only recently started to appreciate its essence. Endophytes may impact plant biology through the production of diverse chemical entities including, but not limited to, plant growth hormones and by modulating the gene expression of defense and other secondary metabolic pathways of the host. Studies have shown differential recruitment of endophytes in endophytic populations of plants growing in the same locations, indicating host specificity and that endophytes evolve in a coordinated fashion with the host plants. Endophytic technology can be employed for the efficient production of agricultural and economically important plants and plant products. The rational application of endophytes to manipulate the microbiota, intimately associated with plants, can help in enhancement of production of agricultural produce, increased production of key metabolites in medicinal and aromatic plants, as well as adaption to new bio-geographic regions through tolerance to various biotic and abiotic conditions. However, the potential of endophytic biology can be judiciously harnessed only when we obtain insight into the molecular mechanism of this unique mutualistic relationship. In this paper, we present a discussion on endophytes, endophytism, their significance, and diverse functions in nature as unraveled by the latest research to understand this universal natural phenomenon.


Subject(s)
Endophytes/physiology , Plants/metabolism , Plants/microbiology , Adaptation, Physiological , Biotechnology/methods , Ecosystem , Endophytes/classification , Endophytes/genetics , Symbiosis
20.
J Parasit Dis ; 39(1): 85-9, 2015 Mar.
Article in English | MEDLINE | ID: mdl-25698867

ABSTRACT

In this study prevalence of chicken coccidiosis in Jammu division were undertaken in both organized and backyard chickens during the year 2010-2011, with an overall prevalence of 39.58 % on examination of 720 faecal samples. Five Eimeria species were identified viz., E. tenella, E. necatrix, E. maxima, E. acervulina and E. mitis. E. tenella was the predominant species in both organized and unorganized farms. The highest prevalence percentage was found in July, 2011 (68.9 %) and the lowest percentage was found in May, 2011 (12.5 %). Coccidial prevalence was found to be 53.61 % in unorganized (backyard poultry birds) as compared to organized birds (25.55 %). Maximum positive cases of coccidian infection was found in monsoon season (60.55 %) and least in summer season (21.66 %). Birds of age 31-45 days showed more prevalence percentage (58.86 %). Higher oocysts count was recorded from July to September with a peak value (38973.00 ± 3075.6) in July and lowest (12914.00 ± 595.48) in the month of May.

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