Overcoming Multidrug Drug Resistance In P-glycoprotein/MDR1 Over-expressing Cell Lines By Marine Derived Compound, CSS | 61754
Clinical Pharmacology & Biopharmaceutics
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This study was performed to investigate the effect of CSS on the p-glycoprotein (p-gp)/MDR1 over-expression which is
likely to bring about multi-drug resistance. The CSS is a marine derivative extracted from a oceanophyte under the East
Sea of Korea. It was chosen from among 178 marine derivatives after preliminary cytotoxicity tests using human glioblastoma
cell line to exclude compounds with severe reactivity and effectiveness screening tests with colon cancer cell line (LS174T). The
viability of LST174T and breast cancer cells (MCF-7) treated with CSS was measured using CellTiter-Glo Luminescent Cell
Viability Assay (G7571, promega) for 120 hours with or without paclitaxel 10 μM. The concentrations of CSS were 0, 0.001,
0.01, 0.03, 0.1, 0.3, 1, 3, 10, 30 μM. To investigate the mechanism, the expression level of p-gp/MDR1 and PXR were assessed
by western blot and RT-PCR with rifampin which induces MDR1 over-expression The CSS 30 μM inhibited the cancer cell
proliferation without killing the cells while cancer cells increased without CSS in the 96-well plates. The numbers of LS174T
treated with paclitaxel 10 μM decreased by 40% without CSS versus with CSS 10 μM. In case of MCF-7, the rates were 0%
without CSS versus 50% with CSS 10 μM. The CSS inhibited the overexpression MDR1 and PXR in the presence of rifampin.
The CSS seems to be a potent chemo-sensitizer overcoming multi drug resistance.
Dong-Hwan Lee has completed his PhD from Yonsei University College of Medicine. He is an Assistant Professor of Clinical Pharmacology in the Department of Clinical Pharmacology and the Manager of the Clinical Pharmacology division of the clinical trial center in Pusan National University Hospital. He has published 13 papers in reputed journals.