School Of Basic And Applied Sciences
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Item DNA barcoding and phylogeny based comparative evaluation of anti-cancer properties of Caulerpa (J V Lamouroux) spp. from Indian coasts(Central University of Punjab, 2019) Mehra, Richa; Bast, Felix and Singh, SandeepA total of 15 Caulerpa samples were collected from Indian coasts and identified based on morphological and molecular data inferred from ITS, 18S, tufA and rbcL. Seven different species viz. C. scalpelliformis, C. racemosa, C. sertularioides, C. verticillata, C. taxifolia, and C. corynephora; and their geographical isolates were identified. Barcode data for these species was generated using aforementioned molecular markers and used for phylogenetic assessment. Phylogenetic trees using Bayesian inference (BI) and Maximum Likelihood (ML) function were generated for each molecular marker. tufA was found to be most suitable marker for the genus Caulerpa, resolving the species into 17 different lineages, with 15 corresponding to already known sections and 2 new lineages. Besides, a database named DbIndAlgae of Indian algae was generated and all the morphological as well as molecular data generated in this study is uploaded on the database. In addition, the phycochemical analysis revealed the presence of alkaloids, terpenoids, steroids, tannins, saponins, flavonoids, and phenols in different Caulerpa species. The selective cytotoxicity of methanolic extracts of Caulerpa (CMEs) was evaluated on MDA-MB-231, T47-D and H1299 cells, and the results revealed significant cytotoxicity of all species. C. racemosa KNY-254 and C. taxifolia TEN-158 were found to be most potent on MDA-MB-231 cells with IC50 value of 0.226 ± 0.004 and 0.246 ± 0.009 µg/µL. The mitochondrial membrane perturbation was revealed by JC-1 and apoptotic cell death was confirmed by Annexin V/FITC staining. CMEs also induced ROS in MDA-MB-231 cells as depicted by DHE, and increased activity of SOD, decreased activity of gluthatione reductase. The CMEs also exhibit anti-invasion activity and inhibited up to 71% migration across the artificially scratched wound in MDA-MB-231, w.r.t. untreated control cells. Moreover, chemical probing of C. racemosa KNY-254 by LC-MS analysis revealed six previously reported and six unreported molecules. The molecular docking analysis revealed weak to moderate interactions with all of the protein targets viz. Bcl2, AMPK, mTOR, BID, PERK, IGF-1R, PI3K, PTP1B and Akt2, known to play important role in cancer cell signaling. Additionally, a moderately positive correlation amongst the phylogeny and anti-cancer activity was observed suggesting that phylogeny might provide cues for anti-cancer activity, subject to further validations.Item Emerging Role of Migration and Invasion Enhancer 1 (MIEN1) in Cancer Progression and Metastasis(Frontiers Media S.A., 2019) Kushwaha, P.P; Gupta, S; Singh, A.K; Kumar, S.Tumor metastasis is a sequential event accounting for numerous cancer-related fatalities worldwide. The process of metastasis serially involves invasion, intravasation, extravasation, and tumor growth at the secondary site. Migration and invasion enhancer 1 (MIEN1) is a membrane associated protein overexpressed in various human cancers. Biological activity of MIEN1 is driven by geranylgeranyltransferase-I mediated prenylation at CAAX motif and methylation of the prenylated protein that anchors MIEN1 into the cellular membrane. Post-translationally modified MIEN1 interacts with Syk kinase and Annexin A2 protein; polymerizes G-actin and stabilizes F-actin filament; induces focal adhesion kinase phosphorylation and decrease cofilin phosphorylation implicated in both invasion and metastasis of different cancer types. In the present review, we discuss the structure, function, and involvement of MIEN1 in cancer progression. We also highlight the future prospects of MIEN1 as an emerging molecule and novel target in cancer cell invasion and metastasis.Item SNHG12: An LncRNA as a Potential Therapeutic Target and Biomarker for Human Cancer(Frontiers Media S.A., 2019) Tamang, S; Acharya, V; Roy, D; Sharma, R; Aryaa, A; Sharma, U; Khandelwal, A; Prakash, H; Vasquez, K.M; Jain, A.Limitations in current diagnostic procedures warrant identification of new methodologies to improve diagnoses of cancer patients. In this context, long non-coding RNAs (lncRNAs) have emerged as stable biomarkers which are expressed abundantly in tumors. Importantly, these can be detected at all stages of tumor development, and thus may provide potential biomarkers and/or therapeutic targets. Recently, we suggested that aberrant levels of lncRNAs can be used to determine the invasive and metastatic potential of tumor cells. Further, direct correlations of lncRNAs with cancer-derived inflammation, metastasis, epithelial-to-mesenchymal transition, and other hallmarks of cancer indicate their potential as biomarkers and targets for cancer. Thus, in this review we have discussed the importance of small nucleolar RNA host gene 12 (SNHG12), a lncRNA, as a potential biomarker for a variety of cancers. A meta-analysis of a large cohort of cancer patients revealed that SNHG12 may also serve as a potential target for cancer-directed interventions due to its involvement in unfolded protein responses, which many tumor cells exploit to both evade immune-mediated attack and enhance the polarization of effector immune cells (e.g., macrophages and T cells). Thus, we propose that SNHG12 may serve as both a biomarker and a druggable therapeutic target with promising clinical potential.Item Anticancer activity of dihydropyrazolo[1,5-c]quinazolines against rat C6 glioma cells via inhibition of topoisomerase II.(Wiley, 2018) Kaur, G; Cholia, RP; Joshi, G; Amrutkar, SM; Kalra, S; Mantha, Anil K.; Banerjee, UC; Kumar, R.The design and synthesis of dihydropyrazolo[1,5‐c]quinazolines (1a–h) as human topoisomerase II (TopoII) catalytic inhibitors are reported. The compounds were investigated for their antiproliferative activity against the C6 rat glial cell line. Two compounds, 1b and 1h, were found to be potent cytotoxic agents against glioma cells and exerted selective TopoII inhibitory activity. Furthermore, the compounds induced alterations in reactive oxygen species levels as measured by DCFDA assay and were found to induce cell cycle arrest at the G1 phase at lower concentrations and profound apoptosis at higher concentrations. The interaction of selected investigational molecules with TopoII was further corroborated by molecular modeling.