Natural Product Sciences

The Korean Society of Pharmacognosy (한국생약학회)
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Diarylbutane-type Lignans from Myristica fragrans (Nutmeg) show the Cytotoxicity against Breast Cancer Cells through Activation of AMP-activated Protein Kinase

  • Le, Thi Van Thu (College of Pharmacy, Chosun University) ;
  • Nguyen, Phi Hung (College of Pharmacy, Chosun University) ;
  • Choi, Hong Seok (College of Pharmacy, Chosun University) ;
  • Yang, Jun-Li (Korea Bioactive Natural Material Bank, Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University) ;
  • Kang, Keon Wook (Korea Bioactive Natural Material Bank, Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University) ;
  • Ahn, Sang-Gun (Department of Pathology, College of Dentistry, Chosun University) ;
  • Oh, Won Keun (Korea Bioactive Natural Material Bank, Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University)
  • Received : 2016.09.10
  • Accepted : 2016.11.18
  • Published : 2017.03.31
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Abstract

In our program to search for new AMP-activated protein kinase (AMPK) activators from plants that exert potential anticancer property, we found that an EtOAc extract of Myristica fragrans (nutmeg) activated AMPK enzyme in human breast cancer MCF-7 cells. Two major diarylbutane-type lignans, macelignan and meso-dihydroguaiaretic acid (MDGA), were isolated as active principles from this extract. Treatment of breast cancer cells with two compounds induced cellular apoptosis, evidenced by cleavage of poly-(ADP-ribose) polymerase (PARP) and Ser 15 phosphorylation of p53. Moreover, macelignan and MDGA significantly inhibited the colony formation of MCF-7 breast cancer cells on soft agar. Intraperitoneal injection of macelignan and MDGA (20 mg/kg) suppressed the tumor growth of 4T1 mammary cancer cells. These results indicate that the chemopreventive effects of two major diarylbutane-type lignans from Myristica fragrans (nutmeg) may be associated with induction of apoptosis presumably through AMPK activation.

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