Satoshi Ueno1, Ryuta Yamazaki2, Takashi Ikeda2, Takashi Yaegashi2, Takeshi Matsuzaki2. 1. Yakult Central Institute for Microbiological Research, Yakult Honsha Co., Ltd., Kunitachi, Tokyo, Japan satoshi-ueno@yakult.co.jp. 2. Yakult Central Institute for Microbiological Research, Yakult Honsha Co., Ltd., Kunitachi, Tokyo, Japan.
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. Copyright
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 humancancer 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 humancolon 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. Copyright
Authors: Jana Kubíčková; Katarína Elefantová; Lucia Pavlikova; Martin Cagala; Mário Šereš; Peter Šafář; Štefan Marchalín; Kamila Ďurišová; Viera Boháčová; Zdena Sulova; Boris Lakatoš; Albert Breier; Petra Olejníková Journal: Molecules Date: 2019-06-05 Impact factor: 4.411