PT  - JOURNAL ARTICLE
AU  - SATOSHI UENO
AU  - RYUTA YAMAZAKI
AU  - TAKASHI IKEDA
AU  - TAKASHI YAEGASHI
AU  - TAKESHI MATSUZAKI
TI  - Antitumor Effect of a Novel Phenanthroindolizidine Alkaloid Derivative Through Inhibition of Protein Synthesis
DP  - 2014 Jul 01
TA  - Anticancer Research
PG  - 3391--3397
VI  - 34
IP  - 7
4099  - http://ar.iiarjournals.org/content/34/7/3391.short
4100  - http://ar.iiarjournals.org/content/34/7/3391.full
SO  - Anticancer Res2014 Jul 01; 34
AB  - 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.