Downregulation of calcineurin activity in cervical carcinoma

Padma, S; Sowjanya, A. Pavani; Poli, Usha Rani; Jain, M.; Rao, BN; Ramakrishna, Gayatri

doi:10.1186/1475-2867-5-7

Cited by 11 publications

(1 citation statement)

References 57 publications

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“…The calcineurin, serine-threonine phosphatase (PP2B), is increasingly being recognized as a commonly activated target in cancer. Activation of calcineurin is implicated in signalling pathways promoting proliferation, migration, and metastasis [44,45] and is involved in apoptosis [46]. Therefore, effect of FSK on PP2B was assessed and upon treatment resulted in downregulation of PP2B in a dose dependent manner.…”

Section: Discussionmentioning

confidence: 99%

Natural Compound Modulates the Cervical Cancer Microenvironment—A Pharmacophore Guided Molecular Modelling Approaches

Rampogu

Doneti

Pawar

et al. 2018

JCM

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Cervical cancer is regarded as one of the major burdens noticed in women next to breast cancer. Although, human papilloma viruses (HPVs) are regarded as the principal causative agents, they require certain other factors such as oestrogen hormone to induce cervical cancer. Aromatase is an enzyme that converts androgens into oestrogens and hindering this enzyme could subsequently hamper the formation of oestrogen thereby alleviating the disease. Accordingly, in the current investigation, a structure based pharmacophore was generated considering two proteins bearing the Protein Data Bank (PDB) codes 3EQM (pharm 1) and 3S7S (pharm 2), respectively. The two models were employed as the 3D query to screen the in-house built natural compounds database. The obtained 51 compounds were escalated to molecular docking studies to decipher on the binding affinities and to predict the quintessential binding modes which were affirmed by molecular dynamics (MD) simulations. The compound has induced dose-dependent down regulation of PP2B, Nitric oxide synthase-2 (NOS2), and Interleukin 6 (IL-6) genes in the HeLa cells and has modulated the expression of apoptotic genes such as Bax, Bcl2, and caspases-3 at different concentrations. These results guide us to comprehend that the identified aromatase inhibitor was effective against the cervical cancer cells and additionally could server as scaffolds in designing new drugs.

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Section: Discussionmentioning

confidence: 99%

Natural Compound Modulates the Cervical Cancer Microenvironment—A Pharmacophore Guided Molecular Modelling Approaches

Rampogu

Doneti

Pawar

et al. 2018

JCM

View full text Add to dashboard Cite

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RETRACTED ARTICLE: Cardiac glycoside induces cell death via FasL by activating calcineurin and NF-AT, but apoptosis initially proceeds through activation of caspases

et al. 2007

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Decrease in caspase activity is a common phenomenon in drug resistance. For effective therapeutic intervention, detection of such agents, which affects other pathway independent of caspases to promote cell death, might be important. Oleandrin, a polyphenolic glycoside induced cell death through activation of caspases in a variety of human tumour cells. In this report we provide evidence that besides caspases activation, oleandrin interacts with plasma membrane, changes fluidity of the membrane, disrupts Na + /K + -ATPase pump, enhances intracellular free Ca 2+ and thereby activates calcineurin. Calcineurin, in turns, activates nuclear transcription factor NF-AT and its dependent genes such as FasL, which induces cell death as a late response of oleandrin. Cell death at early stages is mediated by caspases where inhibitors partially protected oleandrin-mediated cell death in vectortransfected cells, but almost completely in Bcl-xL-overexpressed cells. Overall, our data suggest that oleandrin might be important therapeutic molecule in case of tumors where cell death pathway occurs due to deregulation of caspase-mediated pathway

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Retraction Note to: Cardiac glycoside induces cell death via FasL by activating calcineurin and NF-AT, but apoptosis initially proceeds through activation of caspases

et al. 2013

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Downregulation of calcineurin activity in cervical carcinoma

Cited by 11 publications

References 57 publications

Natural Compound Modulates the Cervical Cancer Microenvironment—A Pharmacophore Guided Molecular Modelling Approaches

Natural Compound Modulates the Cervical Cancer Microenvironment—A Pharmacophore Guided Molecular Modelling Approaches

RETRACTED ARTICLE: Cardiac glycoside induces cell death via FasL by activating calcineurin and NF-AT, but apoptosis initially proceeds through activation of caspases

Retraction Note to: Cardiac glycoside induces cell death via FasL by activating calcineurin and NF-AT, but apoptosis initially proceeds through activation of caspases

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