Modulation of curcumin-induced Akt phosphorylation and apoptosis by PI3K inhibitor in MCF-7 cells

Jaleel Kizhakkayil, Faisal Thayyullathil, Shahanas Chathoth, Abdulkader Hago, Mahendra Patel, Sehamuddin Galadari

    Research output: Contribution to journalArticle

    Abstract

    Curcumin has been shown to induce apoptosis in various malignant cancer cell lines. One mechanism of curcumin-induced apoptosis is through the PI3K/Akt signaling pathway. Akt, also known as protein kinase B (PKB), is a member of the family of phosphatidylinositol 3-OH-kinase regulated Ser/Thr kinases. The active Akt regulates cell survival and proliferation; and inhibits apoptosis. In this study we found that curcumin induces apoptotic cell death in MCF-7 cells, as assessed by MTT assay, DNA ladder formation, PARP cleavage, p53 and Bax induction. At apoptotic inducing concentration, curcumin induces a dramatic Akt phosphorylation, accompanied by an increased phosphorylation of glycogen synthase kinase 3β (GSK3β), which has been considered to be a pro-growth signaling molecule. Combining curcumin with PI3K inhibitor, LY290042, synergizes the apoptotic effect of curcumin. The inhibitor LY290042 was capable of attenuating curcumin-induced Akt phosphorylation and activation of GSK3β. All together, our data suggest that blocking the PI3K/Akt survival pathway sensitizes the curcumin-induced apoptosis in MCF-7 cells.

    Original languageEnglish (US)
    Pages (from-to)476-481
    Number of pages6
    JournalBiochemical and Biophysical Research Communications
    Volume394
    Issue number3
    DOIs
    StatePublished - Apr 9 2010

    Fingerprint

    Phosphorylation
    Curcumin
    MCF-7 Cells
    Phosphatidylinositol 3-Kinases
    Modulation
    Apoptosis
    Glycogen Synthase Kinase 3
    Phosphotransferases
    Cells
    Phosphatidylinositol 3-Kinase
    Proto-Oncogene Proteins c-akt
    Ladders
    Cell death
    Phosphatidylinositols
    Assays
    Cell Survival
    Cell Death
    Chemical activation
    Cell Proliferation
    Cell Line

    Keywords

    • Akt phosphorylation
    • Apoptosis
    • Curcumin
    • MCF-7 cells
    • PI3K inhibitor

    ASJC Scopus subject areas

    • Biophysics
    • Biochemistry
    • Molecular Biology
    • Cell Biology

    Cite this

    Modulation of curcumin-induced Akt phosphorylation and apoptosis by PI3K inhibitor in MCF-7 cells. / Kizhakkayil, Jaleel; Thayyullathil, Faisal; Chathoth, Shahanas; Hago, Abdulkader; Patel, Mahendra; Galadari, Sehamuddin.

    In: Biochemical and Biophysical Research Communications, Vol. 394, No. 3, 09.04.2010, p. 476-481.

    Research output: Contribution to journalArticle

    Kizhakkayil, Jaleel ; Thayyullathil, Faisal ; Chathoth, Shahanas ; Hago, Abdulkader ; Patel, Mahendra ; Galadari, Sehamuddin. / Modulation of curcumin-induced Akt phosphorylation and apoptosis by PI3K inhibitor in MCF-7 cells. In: Biochemical and Biophysical Research Communications. 2010 ; Vol. 394, No. 3. pp. 476-481.
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