Transport of 7-ethyl-10-hydroxycamptothecin (SN-38) by breast cancer resistance protein ABCG2 in human lung cancer cells

Biochem Biophys Res Commun. 2001 Nov 9;288(4):827-32. doi: 10.1006/bbrc.2001.5850.


Overexpression of breast cancer resistance protein (BCRP) ABCG2 reportedly confers cancer cell resistance to camptothecin-based anticancer drugs, such as topotecan and 7-ethyl-10-hydroxycamptothecin (SN-38: the active metabolite of irinotecan). We have recently shown that SN-38-selected PC-6/SN2-5H human lung carcinoma cells overexpressed BCRP with the reduced intracellular accumulation of SN-38 and SN-38-glucuronide (S. Kawabata et al., Biochem. Biophys. Res. Commun. 280, 1216-1223, 2001). In the present study, we have examined whether BCRP transports SN-38 and/or SN-38-glucuronide in vitro, by using plasma membrane vesicles from the parental PC-6 and resistant PC-6/SN2-5H cells, where SN-38 and SN-38-glucuronide accumulation in membrane vesicles was measured by HPLC. Both SN-38 and SN-38-glucuronide were ATP-dependently transported into membrane vesicles prepared from PC-6/SN2-5H cells, whereas no transport activity was observed in membrane vesicles from PC-6 cells. The kinetic parameters of the transport observed in PC-6/SN2-5H vesicles were K(m) = 4.0 microM, V(max) = 714 pmol/mg/min for SN-38 and K(m) = 26 microM, V(max) = 833 pmol/mg/min for SN-38-glucuronide. These findings suggest that BCRP expressed in PC-6/SN2-5H cells transports both SN-38 and SN-38-glucuronide with a higher affinity toward SN-38.

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily G, Member 2
  • ATP-Binding Cassette Transporters / metabolism*
  • Adenosine Triphosphate / metabolism
  • Adenosine Triphosphate / pharmacology
  • Antineoplastic Agents, Phytogenic / metabolism*
  • Antineoplastic Agents, Phytogenic / pharmacokinetics
  • Biological Transport / drug effects
  • Camptothecin / analogs & derivatives*
  • Camptothecin / metabolism*
  • Camptothecin / pharmacokinetics
  • Cell Membrane / drug effects
  • Cell Membrane / metabolism
  • Chromatography, High Pressure Liquid
  • Drug Resistance, Neoplasm / physiology*
  • Glucuronides / metabolism
  • Humans
  • Irinotecan
  • Kinetics
  • Lung Neoplasms / metabolism*
  • Neoplasm Proteins*
  • Secretory Vesicles / drug effects
  • Secretory Vesicles / metabolism
  • Tumor Cells, Cultured


  • 7-ethyl-10-hydroxycamptothecin glucuronide
  • ABCG2 protein, human
  • ATP Binding Cassette Transporter, Subfamily G, Member 2
  • ATP-Binding Cassette Transporters
  • Antineoplastic Agents, Phytogenic
  • Glucuronides
  • Neoplasm Proteins
  • Irinotecan
  • Adenosine Triphosphate
  • Camptothecin