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  • Title: Antitumor effect of a novel phenanthroindolizidine alkaloid derivative through inhibition of protein synthesis.
    Author: Ueno S, Yamazaki R, Ikeda T, Yaegashi T, Matsuzaki T.
    Journal: Anticancer Res; 2014 Jul; 34(7):3391-7. PubMed ID: 24982345.
    Abstract:
    AIM: 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. MATERIALS AND 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. CONCLUSION: YPC-10157 has promising antitumor effects and suggest that its cytotoxic mechanism might involve the inhibition of protein synthesis.
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