title: Antitumor effect of a novel phenanthroindolizidine alkaloid derivative through inhibition of protein synthesis.
abstract: OBJECTIVE
  The present study aimed to determine the antitumor efficacy of a new Phenanthroindolizidine alkaloid (PA) derivative, YPC-10157, and to elucidate its mechanism of action.
  
  
  METHODS
  The in vitro and in vivo antitumor activity of YPC-10157 was evaluated against several human cancer cell lines and mouse xenograft models, respectively. Cell apoptosis was determined by measuring caspase-3/7 activity. The effect on protein synthesis was assessed using an in vitro cell-free translation assay system.
  
  
  RESULTS
  In vitro, YPC-10157 exhibited marked cell growth inhibition and induced apoptosis. In vivo, YPC-10157 had a strong antitumor effect on xenograft models of human colon cancer and leukemia. Moreover, YPC-10157 and its derivatives inhibited protein synthesis and their inhibitory activity on protein synthesis significantly correlated regarding cell growth.
  
  
  CONCLUSIONS
  YPC-10157 has promising antitumor effects and suggest that its cytotoxic mechanism might involve the inhibition of protein synthesis.
authors: Yakult Central Institute for Microbiological Research, Yakult Honsha Co., Ltd., Kunitachi, Tokyo, Japan satoshi-ueno@yakult.co.jp.
authors: Satoshi
authors: S
authors: Ueno
authors: Yakult Central Institute for Microbiological Research, Yakult Honsha Co., Ltd., Kunitachi, Tokyo, Japan.
authors: Ryuta
authors: R
authors: Yamazaki
authors: Yakult Central Institute for Microbiological Research, Yakult Honsha Co., Ltd., Kunitachi, Tokyo, Japan.
authors: Takashi
authors: T
authors: Ikeda
authors: Yakult Central Institute for Microbiological Research, Yakult Honsha Co., Ltd., Kunitachi, Tokyo, Japan.
authors: Takashi
authors: T
authors: Yaegashi
authors: Yakult Central Institute for Microbiological Research, Yakult Honsha Co., Ltd., Kunitachi, Tokyo, Japan.
authors: Takeshi
authors: T
authors: Matsuzaki
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D045325:HCT116 Cells; D018922:HL-60 Cells; D019073:HT29 Cells; D006801:Humans; D026121:Indole Alkaloids / Q000494:pharmacology*; D007212:Indolizines / Q000494:pharmacology*; D061986:MCF-7 Cells; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D010618:Phenanthrolines / Q000494:pharmacology*; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology*; D011897:Random Allocation; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D026121:Indole Alkaloids; D007212:Indolizines; D010618:Phenanthrolines; D011500:Protein Synthesis Inhibitors; C521640:phenanthroindolizidine
keywords: Phenanthroindolizine alcaloid; YPC-10157; antitumor activity; caspase activity