Anticancer Properties of Pomolic Acid-Induced AMP-Activated Protein Kinase Activation in MCF7 Human Breast Cancer Cells

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  • Youn Seog Hyeon
    Department of Surgery, Chungnam National University Hospital
  • Lee Jin Sun
    Department of Surgery, Chungnam National University Hospital
  • Lee Myung Sun
    Regional Cancer Institute, Chungnam National University Hospital
  • Cha Eun Young
    Regional Cancer Institute, Chungnam National University Hospital
  • Thuong Phuong Thien
    Vietnam National Institute of Medicinal Materials
  • Kim Je Ryong
    Department of Surgery, Chungnam National University Hospital Department of Surgery and Cancer Research Institute, Chungnam National University College of Medicine
  • Chang Eil Sung
    Department of Surgery, Chungnam National University Hospital Department of Surgery and Cancer Research Institute, Chungnam National University College of Medicine

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AMP-activated protein kinase (AMPK) is a sensor of cellular energy status found in all eukaryotes. Recent studies indicate that AMPK activation strongly suppresses cell proliferation in tumor cells, which requires high rates of protein synthesis and de novo fatty acid synthesis for their rapid growth. Pomolic acid (PA) has been previously described as being active in inhibiting the growth of cancer cells. In this study, we investigated PA activated AMPK, and this activity was related to proliferation and apoptosis in MCF7 breast cancer cells. PA inhibited cell proliferation and induced sub-G1 arrest, elevating the mRNA levels of the apoptotic genes p53 and p21. PA activated caspase-3, -9, and poly(ADP-ribose) polymerase, and this effect was inhibited by z-VAD-fmk. AMPK activation was increased by treating cells with PA, inactivated by treating cells with a compound C, and co-treatment consisting of PA and aminoimidazole carboxamide ribonucleotide (AICAR) synergistically activated AMPK. These anti-cancer potentials of PA were accompanied by effects on de novo fatty acid synthesis as shown by the decreased expression of fatty acid synthase, and decreased acetyl-CoA carboxylase activation and incorporation of [3H]acetyl-CoA into fatty acids. In addition, PA inhibited key enzymes involved in protein synthesis such as mammalian target of rapamycin (mTOR), 70 kDa ribosomal protein S6 kinase (p70S6K), and eukaryotic translation initiation factor 4E-binding protein 1 (4EBP1). These results suggest that PA exerts anti-cancer properties through the modulation of AMPK pathways and its value as an anti-cancer agent in breast cancer therapy.

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