YAKHAK HOEJI (약학회지)

The Pharmaceutical Society of Korea (대한약학회)
권호 표지

Reversal of Multidrug Resistance by Benzotriazepin Analogues in Cancer Cells

Benzotriazepin 유도체의 암세포에 대한 다약제내성 억제효과

  • Kim Mi Hye (Medicinal Research Division, Korea Research Institute of Chemical Technology) ;
  • Choi Sang Un (Medicinal Research Division, Korea Research Institute of Chemical Technology) ;
  • Choi Eun Jung (Medicinal Research Division, Korea Research Institute of Chemical Technology) ;
  • Kim Sung Soo (Medicinal Research Division, Korea Research Institute of Chemical Technology) ;
  • Choi Jung Kwon (Medicinal Research Division, Korea Research Institute of Chemical Technology) ;
  • Ahn Jin Hee (Medicinal Research Division, Korea Research Institute of Chemical Technology) ;
  • Lee Chong Ock (Medicinal Research Division, Korea Research Institute of Chemical Technology) ;
  • Kwon Kwang Il (College of Pharmacy, Chungnam National University)
  • 김미혜 (한국화학연구원 생명의약연구부) ;
  • 최상운 (한국화학연구원 생명의약연구부) ;
  • 최은정 (한국화학연구원 생명의약연구부) ;
  • 김성수 (한국화학연구원 생명의약연구부) ;
  • 최중권 (한국화학연구원 생명의약연구부) ;
  • 안진희 (한국화학연구원 생명의약연구부) ;
  • 이정옥 (한국화학연구원 생명의약연구부) ;
  • 권광일 (충남대학교 약학대학)
  • Published : 2005.02.01
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Abstract

The occurrence of resistance to chemotherapeutic drugs is a major problem for successful cancer treatment. This resistant phenotype of cancer cell frequently reveals a broad spectrum to structurally and/or functionally unrelated anticancer drugs, termed multidrug resistance (MDR). Overexpression of P-glycoprotein (P-gp), a transmembrane drug efflux pump, is a major mechanism of MDR. Accordingly, considerable effort has been directed towards to development of compounds that inhibit P-gp, reverse the MDR phenotype and sensitize cancer cells to conventional chemotherapy without undesired toxicological effects. In an effort to search for novel MDR reversal agent, we tested the cytotoxicity of paclitaxel, a well-known substrate of P-gp, against P-gp-expressing HCT15 and HCT15/CL02 human colorectal cancer cells in the presence or absence of benzotriazepin analogues, as well as against P-gp-negative A549 human non-small cell lung and SK-OV-3 human ovarian cancer cells in vitro. Among the compounds tested, the agents that have phenyl amide moiety at 3 position remarkably increased the cytotoxicity of paclitaxel against P-gp-expressing cancer cells, but not against P-gp-negative cancer cells. BTZ-15 and BTZ-16 at $4\;{\mu}M$ revealed similar MDR reversal activity to $10\;{\mu}M$ verapamil, a well-known MDR reversal agent.

Keywords

References

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