Browsing by Author "Gopala, Srinivas"

Now showing 1 - 5 of 5
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    Aloe Emodin Induces G2/M Cell Cycle Arrest and Apoptosis via Activation of Caspase-6 in Human Colon Cancer Cells
    (PHARMACOLOGY, 2012)
    Aloe emodin (AE), a natural anthraquinone, is reported to have antiproliferative activity in various cancer cell lines. In this study, we analyzed the molecular mechanisms involved in the growth-inhibitory activity of this hydroxyanthraquinone in colon cancer cell, WiDr. In our observation AE inhibited cell proliferation by arresting the cell cycle at the G2/M phase and inhibiting cyclin B1. AE appreciably induced cell death specifically through the induction of apoptosis and by activating caspases 9/6. Apoptotic execution was found to be solely dependent on caspase-6 rather than caspase-3 or caspase-7. This is the first study indicating that the AE induces apoptosis specifically through the activation of caspase-6. Copyright (C) 2012 S. Karger AG, Basel
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    Aloe emodin inhibits colon cancer cell migration/angiogenesis by downregulating MMP-2/9, RhoB and VEGF via reduced DNA binding activity of NF-kappa B
    (EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES, 2012)
    Aloe emodin (AE), a natural anthraquinone, is reported to have antiproliferative activity in various cancer cell lines. In this study we analyzed molecular mechanisms involved in the antimigratory and antiangiogenic activity of this hydroxy anthraquinone in colon cancer cell, WiDr. Our results show that a relatively non toxic concentration of AE suppressed the phorbol-12-myristyl-13-acetate (PMA) induced migration and invasion of tumor cells. On analysis for the molecules involved in the migration/invasion, we found AE downregulated mRNA expression and promoter/gelatinolytic activity of Matrix Metalloproteinase (MMP)-2/9, as well as the RhoB expression at gene and protein level. It was also a strong inhibitor of Vascular Endothelial Growth Factor (VEGF) expression, promoter activity and endothelial cell migration/invasion and in vitro angiogenesis. AE suppressed the nuclear translocation and DNA binding of NF-kappa B, which is an important transcription factor for controlling MMP-2/9 and VEGF gene expression. Taken together these data indicate that AE target multiple molecules responsible for cellular invasion, migration and angiogenesis. Inhibitory effect on angiogenic and metastatic regulatory processes make AE a sensible candidate as a specific blocker of tumor associated events. (C) 2011 Elsevier B.V. All rights reserved.
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    Insidious role of nitric oxide in migration/invasion of colon cancer cells by upregulating MMP-2/9 via activation of cGMP-PKG-ERK signaling pathways
    (CLINICAL & EXPERIMENTAL METASTASIS, 2012)
    Nitric oxide (NO), an uncharged free radical is implicated in various physiological and pathological processes. The present study is an investigation on the effect of NO on proliferation, apoptosis and migration of colon cancer cells. Colon adenocarcinoma cells, WiDr, were used for the in vitro experiments. Tissues from colon adenocarcinoma, adjacent normal and inflammatory tissue and lymph node with metastasis were evaluated for iNOS, MMP-2/9 and Fra-1/Fra-2. NO increases the proliferation of cancer cells and simultaneously prevents apoptosis. Expression of MMP-2/9, RhoB and Rac-1 was enhanced by NO in a time dependent manner. Further, NO increased phosphorylation of ERK1/2 and induced nuclear translocation of Fra-1 and Fra-2. Electrophoretic mobility shift analysis and use of deletion mutant promoter constructs identified role of AP-1 in NO-mediated regulation of MMP-2/9. iNOS, MMP-2/9, Fra-1 and Fra-2 in normal and colon adenocarcinoma tissues were analyzed and it was found that increased expression of these proteins in cancer when compared to normal provides support to our in vitro findings. The study showed that the NO-cGMP-PKG promotes MMP-2/9 expression by activating ERK-1/2 and AP-1. This study reveals the insidious role of NO in imparting tumor aggressiveness.
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    LRRK2 G2019S mutation does not contribute to Parkinson's disease in South India
    (NEUROLOGY INDIA, 2011)
    Background: The frequency of leucine-rich repeat kinase 2 (LRRK2) G2019S mutation, the most common genetic cause of Parkinson's disease (PD), shows significant variation based on ethnicity. Earlier reports suggest a very low frequency or absence of this mutation in Asians. Objective: To analyze the frequency of LRRK2 G2019S mutation in sporadic and familial cases of PD and normal controls of common ethnicity from South India. Patients and Methods: We used direct sequencing technique of all DNA samples in a clinic-based study of sporadic (n = 100) and familial PD patients (n = 86 index cases) and normal controls (n = 100) of common ethnicity from South India. Results: None among the patients or controls had the G2019S mutation. Conclusion: The founding events that influenced a number of other populations/ethnicities had no impact on the genetic makeup of PD patients from South India. Our findings support the current view that G2019S-associated PD may be population-specific. This has implications in genetic testing for PD and selection of subjects for potential future gene-based therapeutic trials for G2019S carriers in such populations.
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    Nimbolide retards tumor cell migration, invasion, and angiogenesis by downregulating MMP-2/9 expression via inhibiting ERK1/2 and reducing DNA-binding activity of NF-kappa B in colon cancer cells
    (MOLECULAR CARCINOGENESIS, 2012)
    Nimbolide, a plant-derived limonoid has been shown to exert its antiproliferative effects in various cell lines. We demonstrate that nimbolide effectively inhibited proliferation of WiDr colon cancer cells through inhibition of cyclin A leading to S phase arrest. It also caused activation of caspase-mediated apoptosis through the inhibition of ERK1/2 and activation of p38 and JNK1/2. Further nimbolide effectively retarded tumor cell migration and invasion through inhibition of metalloproteinase-2/9 (MMP-2/9) expression, both at the mRNA and protein level. It was also a strong inhibitor of VEGF expression, promoter activity, and in vitro angiogenesis. Finally, nimbolide suppressed the nuclear translocation of p65/p50 and DNA binding of NF-?B, which is an important transcription factor for controlling MMP-2/9 and VEGF gene expression. (C) 2011 Wiley Periodicals, Inc.