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Rapid screening of antineoplastic candidates for the human organic anion transporter OATP1B3 substrates using fluorescent probes
| Title: | Rapid screening of antineoplastic candidates for the human organic anion transporter OATP1B3 substrates using fluorescent probes |
| Authors: | Yamaguchi, Hiroaki Browse this author | | Kobayashi, Minako Browse this author | | Okada, Masahiro Browse this author | | Takeuchi, Toshiko Browse this author | | Unno, Michiaki Browse this author | | Abe, Takaaki Browse this author | | Goto, Junichi Browse this author | | Hishinuma, Takanori Browse this author | | Mano, Nariyasu Browse this author |
| Keywords: | Antineoplastic drugs | | Fluorescent substrate | | Imaging | | OATP1B3 | | Rapid screening |
| Issue Date: | 18-Feb-2008 |
| Publisher: | Elsevier |
| Journal Title: | Cancer Letters |
| Volume: | 260 |
| Issue: | 1-2 |
| Start Page: | 163 |
| End Page: | 169 |
| Publisher DOI: | 10.1016/j.canlet.2007.10.040 |
| PMID: | 18082941 |
| Abstract: | A rapid screening system has been established to extract novel candidates that exhibit potent inhibition of the transport of fluorescent substrate by organic anion transporting polypeptide (OATP) 1B3. OATP1B3 is abundantly expressed in solid digestive organ cancers. Thus, the identification of new substrates leads to novel strategies for effective cancer chemotherapy with minimal adverse effects. We used an automated image acquisition and analysis system (IN Cell Analyzer 1000) to visualize the transport and subsequent accumulation of the fluorescent substrate chenodeoxycholyl-(Nε-NBD)-lysine (CDCA-NBD). Antineoplastic screening demonstrated that five candidates agents, docetaxel, actinomycin D, mitoxantrone, paclitaxel, and SN-38, exhibited potent inhibitory effects on OATP1B3-mediated transport of CDCA-NBD. To clarify if these antineoplastic drugs are substrates for OATP1B3, we performed transport assays in OATP1B3-expressing cells. We determined that SN-38 is a novel substrate for OATP1B3. In conclusion, our results demonstrate that the screening system established in this study is a useful method for the rapid extraction of candidate therapeutic agents from the large numbers of compounds. |
| Type: | article (author version) |
| URI: | http://hdl.handle.net/2115/43859 |
| Appears in Collections: | 薬学研究院 (Faculty of Pharmaceutical Sciences) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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Submitter: 山口 浩明
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