title: Paclitaxel suppresses the viability of breast tumor MCF7 cells through the regulation of EF1α and FOXO3a by AMPK signaling.
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.
authors.affiliation: Department of Anatomy, Korea University College of Medicine, Seoul 136-701, Republic of Korea.
authors.forename: Ji Hae
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Department of Anatomy, Korea University College of Medicine, Seoul 136-701, Republic of Korea.
authors.forename: Jung Ok
authors.initials: JO
authors.lastname: Lee
authors.affiliation: Department of Anatomy, Korea University College of Medicine, Seoul 136-701, Republic of Korea.
authors.forename: Nami
authors.initials: N
authors.lastname: Kim
authors.affiliation: Department of Anatomy, Korea University College of Medicine, Seoul 136-701, Republic of Korea.
authors.forename: Hye Jeong
authors.initials: HJ
authors.lastname: Lee
authors.affiliation: Department of Anatomy, Korea University College of Medicine, Seoul 136-701, Republic of Korea.
authors.forename: Yong Woo
authors.initials: YW
authors.lastname: Lee
authors.affiliation: Department of Anatomy, Korea University College of Medicine, Seoul 136-701, Republic of Korea.
authors.forename: Hyung Ip
authors.initials: HI
authors.lastname: Kim
authors.affiliation: Department of Anatomy, Korea University College of Medicine, Seoul 136-701, Republic of Korea.
authors.forename: Su Jin
authors.initials: SJ
authors.lastname: Kim
authors.affiliation: Department of Anatomy, Korea University College of Medicine, Seoul 136-701, Republic of Korea.
authors.forename: Sun Hwa
authors.initials: SH
authors.lastname: Park
authors.affiliation: Department of Anatomy, Korea University College of Medicine, Seoul 136-701, Republic of Korea.
authors.forename: Hyeon Soo
authors.initials: HS
authors.lastname: Kim
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000096:biosynthesis / Q000235:genetics*; D000620:Aminoimidazole Carboxamide / Q000008:administration & dosage / Q000031:analogs & derivatives; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D002470:Cell Survival / Q000187:drug effects; D005260:Female; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors / Q000096:biosynthesis / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D061986:MCF-7 Cells; D017239:Paclitaxel / Q000008:administration & dosage; D020648:Peptide Elongation Factor 1 / Q000096:biosynthesis / Q000235:genetics*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: C499517:FOXO3 protein, human; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors; D020648:Peptide Elongation Factor 1; C032566:imidazole-4-carboxamide; D000620:Aminoimidazole Carboxamide; D055372:AMP-Activated Protein Kinases; D017239:Paclitaxel