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Article

Rapamycin induces p53-independent apoptosis through the mitochondrial pathway in non-small cell lung cancer cells

  • Authors:
    • Naomi Miyake
    • Hiroki Chikumi
    • Miyako Takata
    • Masaki Nakamoto
    • Tadashi Igishi
    • Eiji Shimizu
  • View Affiliations / Copyright

    Affiliations: Division of Medical Oncology and Molecular Respirology, Department of Multidisciplinary Internal Medicine, Tottori University, 36-1 Nishi-cho, Yonago-shi, Tottori-ken 683-8504, Japan
  • Pages: 848-854
    |
    Published online on: June 12, 2012
       https://doi.org/10.3892/or.2012.1855
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Abstract

The mammalian target of rapamycin (mTOR) is a key kinase acting downstream of growth factor receptor PI3K and AKT signaling, leading to processes resulting in increased cell size and proliferation through translation control. Rapamycin, a specific inhibitor of mTOR, results predominately in G1 cell cycle arrest through translation control and occasionally, cell type-dependent apoptosis by an unknown mechanism. In this study, we investigated the effect and mechanism of action of rapamycin on non-small cell lung cancer (NSCLC) cell lines with p53 mutations. Cell proliferation was evaluated by modified MTT assay. The apoptotic effect of rapamycin was measured by caspase-3 activation and flow cytometric analysis of Annexin V binding. The expression of Bcl-2 and the release of cytochrome c from mitochondria were evaluated by western blotting. We found that rapamycin induced apoptosis in NSCLC cell lines with p53 mutations. Western blot analysis demonstrated that rapamycin downregulates the expression levels of Bcl-2, which leads to increased cytochrome c release from mitochondria and subsequent activation of caspase cascades. These findings suggest that rapamycin induces p53-independent apoptosis through downregulation of Bcl-2 and the mitochondrial pathway in NSCLC cell lines as a novel antitumor mechanism.
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Copy and paste a formatted citation
Spandidos Publications style
Miyake N, Chikumi H, Takata M, Nakamoto M, Igishi T and Shimizu E: Rapamycin induces p53-independent apoptosis through the mitochondrial pathway in non-small cell lung cancer cells. Oncol Rep 28: 848-854, 2012.
APA
Miyake, N., Chikumi, H., Takata, M., Nakamoto, M., Igishi, T., & Shimizu, E. (2012). Rapamycin induces p53-independent apoptosis through the mitochondrial pathway in non-small cell lung cancer cells. Oncology Reports, 28, 848-854. https://doi.org/10.3892/or.2012.1855
MLA
Miyake, N., Chikumi, H., Takata, M., Nakamoto, M., Igishi, T., Shimizu, E."Rapamycin induces p53-independent apoptosis through the mitochondrial pathway in non-small cell lung cancer cells". Oncology Reports 28.3 (2012): 848-854.
Chicago
Miyake, N., Chikumi, H., Takata, M., Nakamoto, M., Igishi, T., Shimizu, E."Rapamycin induces p53-independent apoptosis through the mitochondrial pathway in non-small cell lung cancer cells". Oncology Reports 28, no. 3 (2012): 848-854. https://doi.org/10.3892/or.2012.1855
Copy and paste a formatted citation
x
Spandidos Publications style
Miyake N, Chikumi H, Takata M, Nakamoto M, Igishi T and Shimizu E: Rapamycin induces p53-independent apoptosis through the mitochondrial pathway in non-small cell lung cancer cells. Oncol Rep 28: 848-854, 2012.
APA
Miyake, N., Chikumi, H., Takata, M., Nakamoto, M., Igishi, T., & Shimizu, E. (2012). Rapamycin induces p53-independent apoptosis through the mitochondrial pathway in non-small cell lung cancer cells. Oncology Reports, 28, 848-854. https://doi.org/10.3892/or.2012.1855
MLA
Miyake, N., Chikumi, H., Takata, M., Nakamoto, M., Igishi, T., Shimizu, E."Rapamycin induces p53-independent apoptosis through the mitochondrial pathway in non-small cell lung cancer cells". Oncology Reports 28.3 (2012): 848-854.
Chicago
Miyake, N., Chikumi, H., Takata, M., Nakamoto, M., Igishi, T., Shimizu, E."Rapamycin induces p53-independent apoptosis through the mitochondrial pathway in non-small cell lung cancer cells". Oncology Reports 28, no. 3 (2012): 848-854. https://doi.org/10.3892/or.2012.1855
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