TY - JOUR T1 - Antitumor Effect of a Novel Phenanthroindolizidine Alkaloid Derivative Through Inhibition of Protein Synthesis JF - Anticancer Research JO - Anticancer Res SP - 3391 LP - 3397 VL - 34 IS - 7 AU - SATOSHI UENO AU - RYUTA YAMAZAKI AU - TAKASHI IKEDA AU - TAKASHI YAEGASHI AU - TAKESHI MATSUZAKI Y1 - 2014/07/01 UR - http://ar.iiarjournals.org/content/34/7/3391.abstract N2 - 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. ER -