Rapid screening of antineoplastic candidates for the human organic anion transporter OATP1B3 substrates using fluorescent probes

Hiroaki Yamaguchi, Minako Kobayashi, Masahiro Okada, Toshiko Takeuchi, Michiaki Unno, Takaaki Abe, Junichi Goto, Takanori Hishinuma, Nariyasu Mano

Research output: Contribution to journalArticlepeer-review

57 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)163-169
Number of pages7
JournalCancer Letters
Volume260
Issue number1-2
DOIs
Publication statusPublished - 2008 Feb 18

Keywords

  • Antineoplastic drugs
  • Fluorescent substrate
  • Imaging
  • OATP1B3
  • Rapid screening

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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