In vivo anti-cancer activity of Korean Angelica gigas and its major pyranocoumarin decursin.
We have reported that a 10-herbal traditional formula containing Korean Angelica gigas Nakai (AGN) exerts potent anti-cancer efficacy and identified decursin and decursinol angelate (DA) from AGN as novel anti-androgens. Here, we determined whether AGN would exert in vivo anti-cancer activity and whether decursin or DA could account for its efficacy. The AGN ethanol extract was tested against the growth of mouse Lewis lung cancer (LLC) allograft in syngenic mice or human PC-3 and DU145 prostate cancer xenograft in immunodeficient mice. The pharmacokinetics of decursin and DA were determined. The AGN extract significantly inhibited LLC allograft growth (30 mg/kg) and PC-3 and DU145 xenograft growth (100 mg/kg) without affecting the body weight of the host mice. Biomarker analyses revealed decreased cell proliferation (Ki67, PCNA), decreased angiogenesis (VEGF, microvessel density) and increased apoptosis (TUNEL, cPARP) in treated tumors. Decursin and DA injected intraperitoneally were rapidly hydrolyzed to decursinol. Decursinol and decursin at 50 mg/kg inhibited LLC allograft growth to the same extent, comparable to 30 mg AGN/kg. Therefore the AGN extract possessed significant in vivo anti-cancer activity, but decursin and DA only contributed moderately to that activity, most likely through decursinol.
Lee
Hyo Jeong
HJ
Hormel Institute, University of Minnesota, 801 16th Avenue NE, Austin, MN 55912, USA.
Lee
Hyo Jung
HJ
Lee
Eun Ok
EO
Lee
Jae Ho
JH
Lee
Kuen Sung
KS
Kim
Kwan Hyun
KH
Kim
Sung-Hoon
SH
Lü
Junxuan
J
D000284:Administration, Oral; D029969:Angelica; D020533:Angiogenesis Inhibitors / Q000493:pharmacokinetics / Q000627:therapeutic use; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D001578:Benzopyrans / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002087:Butyrates / Q000493:pharmacokinetics / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D006801:Humans; D007274:Injections, Intraperitoneal; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009369:Neoplasms / Q000188:drug therapy*; D008517:Phytotherapy; D010936:Plant Extracts / Q000493:pharmacokinetics / Q000627:therapeutic use*; D039681:Pyranocoumarins / Q000493:pharmacokinetics / Q000627:therapeutic use
D020533:Angiogenesis Inhibitors; D000972:Antineoplastic Agents, Phytogenic; D001578:Benzopyrans; D002087:Butyrates; D010936:Plant Extracts; D039681:Pyranocoumarins; C101278:decursin