Paclitaxel suppresses the viability of breast tumor MCF7 cells through the regulation of EF1á and FOXO3a by AMPK signaling

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

Research output: Contribution to journalArticle

3 Citations (Scopus)

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-ribofuranosylimidazole.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/EF1¿/FOXO3a signaling pathway.

Original languageEnglish
Pages (from-to)1874-1880
Number of pages7
JournalInternational journal of oncology
Volume47
Issue number5
DOIs
Publication statusPublished - 2015 Nov 1

Keywords

  • Adenosine monophosphate-activated protein kinase
  • Elongation factor 1 α
  • Forkhead box O3a
  • Taxol

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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