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PubMed | Pondicherry Center For Biological science and King Faisal University
Type: Journal Article | Journal: PloS one | Year: 2016

Despite the remarkable progress to fight against breast cancer, metastasis remains the dominant cause of treatment failure and recurrence. Therefore, control of invasiveness potential of breast cancer cells is crucial. Accumulating evidences suggest Aryl hydrocarbon receptor (Ahr), a helix-loop-helix transcription factor, as a promising target to control migration and invasion in breast cancer cells. Thus, an Ahr-based exploration was performed to identify a new Ahr agonist with inhibitory potentials on cancer cell motility.For prediction of potential interactions between Ahr and candidate molecules, bioinformatics analysis was carried out. The interaction of the selected ligand with Ahr and its effects on migration and invasion were examined in vitro using the MDA-MB-231 and T47D cell lines. The silencing RNAs were transfected into cells by electroporation. Expressions of microRNAs (miRNAs) and coding genes were quantified by real-time PCR, and the protein levels were detected by western blot.The in silico and in vitro results identified Flavipin as a novel Ahr agonist. It induces formation of Ahr/Ahr nuclear translocator (Arnt) heterodimer to promote the expression of cytochrome P450 family 1 subfamily A member 1 (Cyp1a1). Migration and invasion of MDA-MB-231 and T47D cells were inhibited with Flavipin treatment in an Ahr-dependent fashion. Interestingly, Flavipin suppressed the pro-metastatic factor SRY-related HMG-box4 (Sox4) by inducing miR-212/132 cluster. Moreover, Flavipin inhibited growth and adhesion of both cell lines by suppressing gene expressions of B-cell lymphoma 2 (Bcl2) and integrin4 (ITGA4).Taken together, the results introduce Flavipin as a novel Ahr agonist, and provide first evidences on its inhibitory effects on cancer cell motility, suggesting Flavipin as a candidate to control cell invasiveness in breast cancer patients.


PubMed | Cryovault Biotech india. and Pondicherry Center for Biological science
Type: | Journal: MicroRNA (Shariqah, United Arab Emirates) | Year: 2016

MicroRNAs (miRNAs) are non- coding RNAs and known to control a broad range of biological functions such as cellular proliferation, differentiation and programmed cell death. Recent reports also showed that miRNAs can act as oncogenes or tumor suppressors, plays important roles in cancer initiation and progression. Expressed sequence tags (ESTs) are random single pass sequence reads, which displays the condition/tissue specific transcripts (coding and non-coding) of an organism. In the present study we have applied bioinformatics approach to identify miRNA from prostate cancer EST resource, the expressions were analyzed by quantitative reverse transcription PCR (qRT-PCR) and the obtained results were explained in detail.


Saravanan S.,Entomology Research Institute | Hairul Islam V.I.,Entomology Research Institute | Hairul Islam V.I.,Pondicherry Center for Biological science | Thirugnanasambantham K.,Pondicherry Center for Biological science | And 4 more authors.
Inflammation Research | Year: 2014

Objective and design: Rheumatoid arthritis is a chronic inflammatory and autoimmune disease that leads to aggressive joint cartilage and bone destruction. Swertiamarin is a secoiridoid glycoside found in Enicostema axillare (Lam) A. Raynal, a medicinal plant used in the Indian system of traditional medicine. In the present study, the potential of swertiamarin was evaluated in IL-1β induced fibroblast-like synoviocytes (FLS). Methods: The FLS were isolated from Freund's Complete Adjuvant induced arthritic (AA) rats and cultured with IL-1β. The normal FLS and AA-FLS were cultured and used for subsequent experiment in fibroblastic morphology form. The efficacy of swertiamarin (10-50 μg/ml) was evaluated on mRNA and protein expression levels of inflammatory and osteoclastogenesis mediators. The efficacy was also evaluated on p38 MAPKα levels with time course studies (2, 4, 6, 8 and 12 h). Results: IL-1β induced cell proliferation (149.46 ± 13.73 %) and NO production (162.03 ± 11.03 %) in AA-FLS; treatment with swertiamarin controlled proliferation (82.77 ± 4.22 %) and NO production (82.06 ± 3.91 % at 50 μg/ml) in a dose-dependent manner. It also significantly (P < 0.05) modulated the expression of apoptotic marker (caspase 3), proinflammation mediators (TNFα, IL-6, PGE2, COX-2, iNOS, MMPs) and osteoclastogenic mediator (RANKL) at both the mRNA and protein levels. Treatment with swertiamarin inhibited the levels of p38 MAPKα in a dose-dependent manner and also significantly (P < 0.05) attenuated the release of the same in time dependent mode. Conclusion: These findings suggest that treatment with swertiamarin attenuated IL-1β induced FLS, and it revealed anti-inflammatory potential by attenuating aggressive FLS. © 2014 Springer.


Thirugnanasambantham K.,State Bio control Laboratory | Thirugnanasambantham K.,Pondicherry Center for Biological science | Durairaj S.,Pondicherry Center for Biological science | Saravanan S.,Pondicherry Center for Biological science | And 3 more authors.
Plant Molecular Biology Reporter | Year: 2015

Plants are nonmotile and are easily affected by both biotic and abiotic stresses. Plants have evolved themselves at both cellular and molecular level to fight against stress. Transcription factors are important among the stress-responsive genes, and their protein products are known to regulate the expression of other stress-responsive genes via binding to the regulatory elements. Among the plant transcription factors, ethylene response factor (ERF) is one of the largest subfamilies of Apetala2 (AP2)/ERF transcription factor family and is characterized with single AP2 domain. ERFs are a double-edged sword; though most of the ERFs are activators of stress-responsive genes, certain ERF could act as repressor, and this phenomenon of ERF has been well discussed in this review. Further, the expression of ERFs may be ethylene dependent or independent and is regulated by feedback mechanism. Apart from above regulation mechanism, expressions of ERFs are post-transcriptionally regulated by microRNAs (miRNAs), and miRNA expressions are in turn regulated by ERFs. The present review highlights the importance of ERFs in plant stress management and complexity in regulation of ERF expression in response to various stresses. © 2014, Springer Science+Business Media New York.


Sekar D.,Pondicherry Center for Biological science | Hairul Islam V.I.,Pondicherry Center for Biological science | Thirugnanasambantham K.,Pondicherry Center for Biological science | Saravanan S.,Pondicherry Center for Biological science | Saravanan S.,Entomology Research Institute
Tumor Biology | Year: 2014

The critical role of microRNAs (miRNAs) in cell differentiation, homeostasis and cancer development has been extensively discussed in recent publications. The microRNAs with RISC enzyme complex allow it to find its complementary sequence, which is usually located in the 3′-untranslated region (UTR) of the target messenger RNA (mRNA). This is followed by inhibition of protein translation or promotion, resulting in degradation of the target gene. miR-21 has been mapped at chromosome 17q23.2, where it overlaps with the protein coding gene vacuole membrane protein 1 (VMP1), a human homologue of rat vacuole membrane protein. Recent evidence indicates that miR-21 plays a vital role in tumour cell proliferation, apoptosis and invasion. The inhibition of miR-21 may induce cell cycle arrest and increased chemosensitivity to anticancer agents, providing evidence that miR-21 functions as an oncogene in human cancer. Increased expression levels of miR-21 were observed in tumours arising from diverse tissue types. This also includes tumours of haematological origin, such as chronic lymphatic leukaemia, diffuse large B cell lymphomas (DLBCLs), acute myeloid leukaemia and Hodgkin lymphomas. Recently, it has been shown that high levels of B cell activation were induced by miR-21 in circulating B cells and are seen in HIV-infected individual. Notably, miR-21 is overexpressed in activated B cells, suggesting its assistance in maintaining B cell hyperactivation, which plays a pivotal role in HIV-infected cells. Therefore, miR-21 can be considered as a powerful biomarker in HIV-related lymphomas. The number of studies related to the role of miR-21 in HIV-related lymphomas is sparse; therefore, this mini review highlights the recent publications related to clinical impact and significance of miR-21, specifically in HIV- and non-HIV-related lymphomas. © 2014, International Society of Oncology and BioMarkers (ISOBM).


Saravanan S.,Entomology Research Institute | Hairul Islam V.I.,Entomology Research Institute | Hairul Islam V.I.,Pondicherry Center for Biological science | Prakash Babu N.,Entomology Research Institute | And 7 more authors.
European Journal of Pharmaceutical Sciences | Year: 2014

Rheumatoid arthritis (RA) is an autoimmune and chronic inflammatory disease that leads to pannus formation followed by severe joint destruction, characterized by synovial hyperplasia, inflammation and angiogenesis. Swertiamarin is a secoiridoid glycoside that is used as an anti-inflammatory compound, mainly found in Enicostema axillare (Lam) A. Raynal, a medicinal plant used in Indian system of traditional medicine. In the present study, the effect of swertiamarin was evlauated in experimental adjuvant arthritis animal model by the estimation of biochemical (paw thickness, lysosomal enzymes, and urinary degradative products) parameters, proinflammatory cytokines and enzymes along with histopathological and radiographic observations. The proteins of phosphorylated NF-κB/IκB and JAK2/STAT3 transcription factors were also quantified from experimental animals as well as LPS induced RAW 264.7 macrophage cells. In in silico analysis, swertiamarin was docked with proinflammatory enzymes to confirm its potential. The administration of swertiamarin (2, 5, 10 mg/kg bw) significantly (P ≤ 0.05) inhibited the levels of paw thickness, lysosomal enzymes and increased the body weight of experimental animals in a dose dependent manner. In molecular analysis, the treatment decreased the release of proinflammatory cytokines (IL1, TNF, IL-6) and proangiogenic enzymes (MMPs, iNOS, PGE2, PPARγ and COX-2); and also significantly (P ≤ 0.05) increased the levels of antiinflammatory proteins (IL-10, IL-4) when compared to the disease groups. The swertiamarin treatment significantly (P ≤ 0.05) inhibited the release of NF-κB p65, p-IκBα, p-JAK2 and p-STAT3 signaling proteins levels on both experimental animals and LPS induced cells. Histopathological and radiological analysis evidenced the curative effect of swertiamarin on bone destruction. The docking studies of swertiamarin on proinflammatory enzymes supported the results from the in vivo experiments. Thus the swertiamarin inhibited the development of arthritis by modulating NF-κB/IκB and JAK2/STAT3 signaling. These findings suggested that swertiamarin acted as an anti-rheumatic agent. 7copy; 2014 Elsevier B.V. All rights reserved.


Thirugnanasambantham K.,Pondicherry Center for Biological science | Hairul-Islam V.I.,Pondicherry Center for Biological science | Saravanan S.,Entomology Research Institute | Subasri S.,Pondicherry Center for Biological science | And 3 more authors.
Applied Biochemistry and Biotechnology | Year: 2013

MicroRNAs (miRNAs) are small, noncoding RNAs that play key roles in regulating gene expression in animals, plants, and viruses, which involves in biological processes including development, cancer, immunity, and host-microorganism interactions. In this present study, we have used the computational approach to identify potent miRNAs involved in Anopheles gambiae immune response. Analysis of 217,261 A. gambiae ESTs and further study of RNA folding revealed six new miRNAs. The minimum free energy of the predicted miRNAs ranged from -27.2 to -62.63 kcal/mol with an average of -49.38 kcal/mol. While its A + U % ranges from 50 to 65 % with an average value of 57.37 %. Phylogenetic analysis of the predicted miRNAs revealed that aga-miR-277 was evolutionary highly conserved with more similarity with other mosquito species. Observing further the target identification of the predicted miRNA, it was noticed that the aga-miR-2304 and aga-miR-2390 are involved in modulation of immune response by targeting the gene encoding suppressin and protein prophenoloxidase. Further detailed studies of these miRNAs will help in revealing its function in modulation of A. gambiae immune response with respect to its parasite. © 2013 Springer Science+Business Media New York.


PubMed | State Bio control Laboratory, Narayana Medical College and Hospital, Pondicherry Center for Biological science, Cryovault Biotech India Pvt. Ltd and Pondicherry University
Type: Journal Article | Journal: Clinics and research in hepatology and gastroenterology | Year: 2016

Despite promising developments of treatment, the mortality due to gastric cancer remains high and the mechanisms of gastric cancer initiation and the development also remains elusive. It has been reported that patients with positive serologic tests for H.pylori have a higher risk of the development of gastric cancer. microRNAs (miRNAs) are short non-coding RNA molecules consisting of 21-25 nucleotides (nt) in length. The miRNAs silence their cognate target genes by inhibiting mRNA translation or degrading the mRNA molecules by binding to their 3-untranslated (UTR) regions and plays a very important role in cancer biology. Recent evidences indicate that miR-21 is overexpressed in tumour tissue, including gastric cancer and plays a vital role in tumour cell proliferation, apoptosis, invasion and angiogenesis. Elevated levels of miR-21 is associated with downregulation of tumour suppressor genes, such as programmed cell death 4 (PDCD4), tissue inhibitor of metalloproteinase 3, phosphatase and tensin homolog (PTEN), tropomyosin 1, ras homolog gene family member B, and maspin. Silencing of miR-21 through the use of a miR-21 inhibitor affected cancer cell viability, induced cell cycle arrest and increased chemosensitivity to anticancer agents indicating that miR-21 functions as an oncogene. Although an increased expression level of miR-21 has been observed in gastric cancer, studies related to the role of miR-21 in gastric cancer progression is very limited. The main thrust of this mini review is to explain the potency of miR-21 as a prognostic and/or diagnostic biomarker and as a new target for clinical therapeutic for interventions of gastric cancer progression.


PubMed | King Saud University, Entomology Research Institute and Pondicherry Center for Biological science
Type: | Journal: Environmental science and pollution research international | Year: 2016

The hydrodistillated essential oil of Atalantia monophylla was subjected to GC-MS. Forty compounds were presented in the essential oil. Eugenol (19.76%), sabinene (19.57%), 1,2-dimethoxy-4-(2-methoxyethenyl) benzene (9.84%), beta-asarone (7.02%) and methyl eugenol (5.52%) were found the predominant compounds. The oil was tested for fumigant toxicity and repellent activity against Callosobruchus maculatus and Sitophilus oryzae. The development stage of C. maculatus fecundity, adult emergence and also ovicidal activities were studied by the treatment of A. monophylla oil. The oil exhibited considerable fumigation toxicity (70.22%), repellent activity (85.24%) and ovicidal activity (100%) against C. maculatus. The oil significantly reduced the protein, esterase, acetylcholinesterase and glutathione S-transferase on C. maculatus and S. oryzae. It can be considered that A. monophylla has a potential insecticide against stored product pests.


PubMed | Pondicherry Center for Biological science, CSIR - Central Leather Research Institute and Government Anna Hospital Campus
Type: | Journal: European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences | Year: 2016

Ulcerative colitis, particularly the chronic persistent form is characterized by the presence of active inflammation and extensive areas of ulceration in the colonic mucosa. The existing treatment protocol aims at only reducing intestinal inflammation, rather than targeting mucosal ulceration. In this study, type I collagen and its daughter peptides called collagen hydrolysate, highly popular reconstructive materials for tissue engineering applications, are hypothesized as healing matrices to target the recuperation of internal mucosal ulceration. The clinical assessments on day 10 of dextran sodium sulfate induced colitis in mice model revealed that both the collagen (1.560.29) and collagen hydrolysate treatments (1.330.33) showed a significant reduction in the rectal bleeding compared to the reference mesalamine treatment (2.500.33) and untreated negative control (2.400.40). VEGF, a potent angiogenic growth factor, over expressed during UC was down-regulated by collagen hydrolysate (1.060.25) and collagen (1.760.45) to a greater extent than by mesalamine (2.590.51) and untreated control (4.170.15). The down-regulation of proinflammatory cytokines such as TNF-, IL-1, and IL-6 also follows the same pattern. Histological observations were in accordance with the clinical indicators. Both collagen and collagen hydrolysate treatments showed significant reduction in mucosal damage score and facilitated faster regeneration of damaged mucosa.

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