Oleandrin induces apoptosis in human, but not in murine cells

Dephosphorylation of Akt, expression of FasL, and alteration of membrane fluidity

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

    Research output: Contribution to journalArticle

    39 Citations (Scopus)

    Abstract

    Common practice to evaluate the efficacy of any compound as drug is done in cell-based in vitro system followed by in vivo murine model prior to clinical trial in human. Cardiac glycosides are very effective to kill human cells, but not murine cells. In this report, we describe the comparative molecular mechanism of oleandrin, a cardiac glycoside action in human and murine cells. Treatment with oleandrin facilitated nuclear translocation of FKHR in human, but not murine cells by dephosphorylating Akt. It activated MAPK and JNK in human, but not in murine cells and also induced expression of FasL leads to apoptosis in human cells as detected by assaying caspases activation, PARP cleavage, nuclear fragmentation, and annexin staining. Oleandrin interacted with human plasma membrane as evaluated by HPLC, altered its fluidity as detected by DPH binding, inhibited Na+/K+-ATPase activity, and increased intracellular free Ca2+ level followed by calcineurin activity only in human, but not in murine cells. Results suggest that human plasma membrane might be different than murine, which interact with oleandrin that disturb Na+/K+-ATPase pump resulting in the calcification followed by induction of Ca2+-dependent cellular responses such as apoptosis.

    Original languageEnglish
    Pages (from-to)2292-2302
    Number of pages11
    JournalMolecular Immunology
    Volume44
    Issue number9
    DOIs
    Publication statusPublished - 03-2007

    Fingerprint

    Membrane Fluidity
    Apoptosis
    Cardiac Glycosides
    Cell Membrane
    Annexins
    oleandrin
    Calcineurin
    Caspases
    High Pressure Liquid Chromatography
    Clinical Trials
    Staining and Labeling

    All Science Journal Classification (ASJC) codes

    • Immunology
    • Molecular Biology

    Cite this

    Raghavendra, Pongali B. ; Sreenivasan, Yashin ; Manna, Sunil K. / Oleandrin induces apoptosis in human, but not in murine cells : Dephosphorylation of Akt, expression of FasL, and alteration of membrane fluidity. In: Molecular Immunology. 2007 ; Vol. 44, No. 9. pp. 2292-2302.
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    Oleandrin induces apoptosis in human, but not in murine cells : Dephosphorylation of Akt, expression of FasL, and alteration of membrane fluidity. / Raghavendra, Pongali B.; Sreenivasan, Yashin; Manna, Sunil K.

    In: Molecular Immunology, Vol. 44, No. 9, 03.2007, p. 2292-2302.

    Research output: Contribution to journalArticle

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