Details

Autor(en) / Beteiligte

• Nakamura, Takashi
• Oka, Mikio
• Aizawa, Kikuo
• Soda, Hiroshi
• Fukuda, Minoru
• Terashi, Kenji
• Ikeda, Koki
• Mizuta, Yohei
• Noguchi, Yuji
• Kimura, Yoshimitsu
• Tsuruo, Takashi
• Kohno, Shigeru

Titel

Direct Interaction between a Quinoline Derivative, MS-209, and Multidrug Resistance Protein (MRP) in Human Gastric Cancer Cells

Ist Teil von

• Biochemical and biophysical research communications, 1999-02, Vol.255 (3), p.618-624

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

1999

Quelle

Elsevier Journal Backfiles on ScienceDirect (DFG Nationallizenzen)

Beschreibungen/Notizen

• MS-209 is a novel quinoline derivative reversing P-glycoprotein-mediated multidrug resistance (MDR). We investigated the interaction between MS-209 and multidrug resistance protein (MRP) in MRP-overexpressing human gastric cancer cells. We measured [3H]leukotriene C4uptake into the membrane vesicles of the cells and intracellular calcein and [3H]vincristine accumulation with or without MS-209. In muti-drug-resistant MKN45R0.8 cells selected by doxorubicin, MS-209 dose dependently reduced MRP-mediated [3H]leukotriene C4uptake and increased calcein accumulation. In both resistant and unselected cell lines expressing the MRP gene, MS-209 increased [3H]vincristine accumulation in proportion with the level of MRP mRNA expression and enhanced the cytotoxicity of etoposide, doxorubicin, and vincristine. The reversal effects correlated with the level of MRP mRNA expression in these cells. Our results indicate that MS-209 effectively reverses intrinsic and acquired MRP-mediated MDR of gastric cancer cells by interacting directly with MRP.