Inhibition of induced autophagy increases apoptosis of Nara-H cells

  • Authors:
    • Osamu Nakamura
    • Toshiaki Hitora
    • Toshihiro Akisue
    • Teruya Kawamoto
    • Yoshiki Yamagami
    • Tetsuji Yamamoto
  • View Affiliations

  • Published online on: July 29, 2011     https://doi.org/10.3892/ijo.2011.1148
  • Pages: 1545-1552
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Abstract

Inhibition of the mTOR signaling pathway promotes initiation of autophagy. However, recent studies indicate that autophagy is a self-defense mechanism of cancer cells that are subjected to anti-tumor agents and that blocking autophagy can trigger apoptosis. Here, we examined the effects of an mTOR inhibitor, temsirolimus, on a malignant fibrous histiocytoma (MFH) cell line, Nara-H cells, and the effect of suppressing autophagy on the induction of apoptosis in these MFH cells. In Nara-H cells, we examined the effects of temsirolimus treatment on cell proliferation using the CellTiter 96® AQueous One Solution Cell Proliferation Assay and on phosphorylation of mTOR pathway components and autophagy using Western blot-based assays. Furthermore, we examined the effects of temsirolimus with or without 3-methyladenine (3-MA) on induction of apoptosis using fluorescent microscopic analysis. In Nara-H cells, temsirolimus treatment inhibited cell proliferation, suppressed phosphorylation of mTOR pathway components, and induced autophagy as assessed by LC-3 II expression. Moreover, treatment with a combination of temsirolimus and 3-MA induced apoptosis in Nara-H cells. Apparently, simultaneous inhibition of autophagy and mTOR induced apoptosis in Nara-H cells because inhibition of autophagy prevented the cells from protecting themselves from the effects of the inhibition of mTOR. Therefore, a combination therapy that includes an mTOR inhibitor and an autophagy inhibitor (temsirolimus and 3-MA, respectively) may effectively treat MFH by inducing apoptosis in tumor cells.

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December 2011
Volume 39 Issue 6

Print ISSN: 1019-6439
Online ISSN:1791-2423

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APA
Nakamura, O., Hitora, T., Akisue, T., Kawamoto, T., Yamagami, Y., & Yamamoto, T. (2011). Inhibition of induced autophagy increases apoptosis of Nara-H cells. International Journal of Oncology, 39, 1545-1552. https://doi.org/10.3892/ijo.2011.1148
MLA
Nakamura, O., Hitora, T., Akisue, T., Kawamoto, T., Yamagami, Y., Yamamoto, T."Inhibition of induced autophagy increases apoptosis of Nara-H cells". International Journal of Oncology 39.6 (2011): 1545-1552.
Chicago
Nakamura, O., Hitora, T., Akisue, T., Kawamoto, T., Yamagami, Y., Yamamoto, T."Inhibition of induced autophagy increases apoptosis of Nara-H cells". International Journal of Oncology 39, no. 6 (2011): 1545-1552. https://doi.org/10.3892/ijo.2011.1148