Paclitaxel suppresses the viability of breast tumor MCF7 cells through the regulation of EF1α and FOXO3a by AMPK signaling

  • Authors:
    • Ji Hae Kim
    • Jung Ok Lee
    • Nami Kim
    • Hye Jeong Lee
    • Yong Woo Lee
    • Hyung Ip Kim
    • Su Jin Kim
    • Sun Hwa Park
    • Hyeon Soo Kim
  • View Affiliations

  • Published online on: September 10, 2015     https://doi.org/10.3892/ijo.2015.3153
  • Pages: 1874-1880
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Abstract

Paclitaxel (Taxol), a potent drug of natural origin isolated from the bark of the Pacific yew, is widely used for treating ovarian, lung and breast cancers. Currently, there is little information regarding the specific mechanism underlying the anticancer activity of paclitaxel. In the present study, we found that 5-amino-1-β-D-ribofuranosyl-imidazole‑4‑carboxamide (AICAR), a well-known activator of adenosine monophosphate (AMP)-activated protein kinase (AMPK), downregulated the protein and mRNA levels of elongation factor 1 α (EF1α) in breast cancer MCF7 cells. Paclitaxel increased the phosphorylation of AMPK and also downregulated the expression of EF1α in MCF7 cells. In addition, paclitaxel increased the expression, as well as the phosphorylation of forkhead box O3a (FOXO3a). Phosphorylation of FOXO3a was suppressed in the presence of compound C, a specific AMPK inhibitor, suggesting the involvement of AMPK in paclitaxel-induced FOXO3a phosphorylation. The induction and phosphorylation of FOXO3a by paclitaxel were not observed in EF1α and AMPK knockdown cells. Co-treatment with AICAR resulted in increased susceptibility of cancer cells to paclitaxel-induced suppression of their viability and further enhanced paclitaxel‑induced FOXO3a phosphorylation. These results suggest that the antitumor effects of paclitaxel in breast cancer are mediated by activation of the AMPK/EF1α/FOXO3a signaling pathway.
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November-2015
Volume 47 Issue 5

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

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Spandidos Publications style
Kim JH, Lee JO, Kim N, Lee HJ, Lee YW, Kim HI, Kim SJ, Park SH and Kim HS: Paclitaxel suppresses the viability of breast tumor MCF7 cells through the regulation of EF1α and FOXO3a by AMPK signaling. Int J Oncol 47: 1874-1880, 2015.
APA
Kim, J.H., Lee, J.O., Kim, N., Lee, H.J., Lee, Y.W., Kim, H.I. ... Kim, H.S. (2015). Paclitaxel suppresses the viability of breast tumor MCF7 cells through the regulation of EF1α and FOXO3a by AMPK signaling. International Journal of Oncology, 47, 1874-1880. https://doi.org/10.3892/ijo.2015.3153
MLA
Kim, J. H., Lee, J. O., Kim, N., Lee, H. J., Lee, Y. W., Kim, H. I., Kim, S. J., Park, S. H., Kim, H. S."Paclitaxel suppresses the viability of breast tumor MCF7 cells through the regulation of EF1α and FOXO3a by AMPK signaling". International Journal of Oncology 47.5 (2015): 1874-1880.
Chicago
Kim, J. H., Lee, J. O., Kim, N., Lee, H. J., Lee, Y. W., Kim, H. I., Kim, S. J., Park, S. H., Kim, H. S."Paclitaxel suppresses the viability of breast tumor MCF7 cells through the regulation of EF1α and FOXO3a by AMPK signaling". International Journal of Oncology 47, no. 5 (2015): 1874-1880. https://doi.org/10.3892/ijo.2015.3153