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

Cancer Lett. 2008 Feb 18;260(1-2):163-9. doi: 10.1016/j.canlet.2007.10.040. Epub 2007 Dec 20.


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-(Nepsilon-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.

Publication types

  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / metabolism
  • Antineoplastic Agents / pharmacology*
  • Camptothecin / analogs & derivatives*
  • Camptothecin / metabolism
  • Camptothecin / pharmacology
  • Chenodeoxycholic Acid / analogs & derivatives*
  • Chenodeoxycholic Acid / metabolism
  • Dactinomycin / pharmacology
  • Docetaxel
  • Fluorescent Dyes / metabolism*
  • Humans
  • Irinotecan
  • Kinetics
  • Lysine / analogs & derivatives*
  • Lysine / metabolism
  • Mitoxantrone / pharmacology
  • Organic Anion Transporters, Sodium-Independent / antagonists & inhibitors*
  • Organic Anion Transporters, Sodium-Independent / genetics
  • Organic Anion Transporters, Sodium-Independent / metabolism
  • Paclitaxel / pharmacology
  • Signal Processing, Computer-Assisted
  • Solute Carrier Organic Anion Transporter Family Member 1B3
  • Spectrometry, Fluorescence
  • Taxoids / pharmacology
  • Transfection


  • Antineoplastic Agents
  • Fluorescent Dyes
  • Organic Anion Transporters, Sodium-Independent
  • SLCO1B3 protein, human
  • Solute Carrier Organic Anion Transporter Family Member 1B3
  • Taxoids
  • chenodeoxycholyl-nitrobenzoxadiazolyl-lysine
  • Chenodeoxycholic Acid
  • Docetaxel
  • Dactinomycin
  • Irinotecan
  • Mitoxantrone
  • Lysine
  • Paclitaxel
  • Camptothecin