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RETRACTED ARTICLE: Cardiac glycoside induces cell death via FasL by activating calcineurin and NF-AT, but apoptosis initially proceeds through activation of caspases

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This article was retracted on 12 May 2013

Abstract

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 Ca2+ 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 vector-transfected 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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Abbreviations

ALLN:

N-acetylleucylleucylnorleucinal

BAPTA-AM:

1,2-bis (2-aminophenoxy) ethane-N,N,N′,N′-tetra acetic acid - acetoxymethyl ester

CsA:

cyclosporin A

DAPI:

4′, 6-diamidino-2-phenylindole

DPH:

diphenylhexatriene

GFP:

green fluorescent peptide

FITC:

fluorescein isothiocyanate

MTT:

3-(4,5-dimethyl-2-thiozolyl)-2,5-diphenyl-2H-tetrazolium bromide

NF-AT:

nuclear factor of activated T lymphocytes

PE:

phycoerythrin

PI:

propidium iodide

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Author information

Authors and Affiliations

  1. Laboratory of Immunology, Centre for DNA Fingerprinting & Diagnostics, Nacharam, Hyderabad, 500076, India

    Pongali B. Raghavendra, Yashin Sreenivasan & Sunil K. Manna

  2. Department of Biology, Texas Southern University, Houston, Texas, 77004, USA

    Govindarajan T. Ramesh

Authors
  1. Pongali B. Raghavendra
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  2. Yashin Sreenivasan
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  3. Govindarajan T. Ramesh
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  4. Sunil K. Manna
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Corresponding author

Correspondence to Sunil K. Manna.

Additional information

This article has been retracted at the request of the Centre for DNA Fingerprinting and Diagnostics as it contains manipulated figures.

The retraction note to this article can be found online at http://dx.doi.org/10.1007/s10495-013-0853-3.

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Raghavendra, P.B., Sreenivasan, Y., Ramesh, G.T. et al. RETRACTED ARTICLE: Cardiac glycoside induces cell death via FasL by activating calcineurin and NF-AT, but apoptosis initially proceeds through activation of caspases. Apoptosis 12, 307–318 (2007). https://doi.org/10.1007/s10495-006-0626-3

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  • DOI: https://doi.org/10.1007/s10495-006-0626-3

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