Open AccessBromocriptine Reverses P‐Glycoprotein‐mediated Multidrug Resistance in Tumor Cells
Author(s) -
Shiraki Nobuaki,
Okamura Keiko,
Tokunaga Jin,
Ohmura Takafumi,
Yasuda Kazuto,
Kawaguchi Takeo,
Hamada Akinobu,
Nakano Masahiro
Publication year - 2002
Publication title -
japanese journal of cancer research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 0910-5050
DOI - 10.1111/j.1349-7006.2002.tb01260.x
Subject(s) - bromocriptine , p glycoprotein , multiple drug resistance , pharmacology , efflux , vinblastine , doxorubicin , cytotoxicity , etoposide , cytotoxic t cell , biology , medicine , cancer research , endocrinology , drug resistance , chemotherapy , biochemistry , in vitro , prolactin , hormone , microbiology and biotechnology
One of the most important causes of anticancer treatment failure is the development of multidrug resistance (MDR). The main characteristics of tumor cells displaying the MDR phenomena are cross‐resistance to structurally unrelated cytotoxic drugs having different mechanisms of action and the overexpression of the MDR1 gene, which encodes a transmembrane glycoprotein named P‐ glycoprotein (P‐gp). This study evaluated whether bromocriptine, a D 2 dopaminergic receptor agonist, influenced anticancer drug cytotoxicity and P‐gp activity in a P‐gp‐expressing cell line compared to a non‐expressing subline. The K i values for P‐gp of cyclosporine and verapamil were 1.09 and 540 μ M , respectively, and that of bromocriptine was 6.52 μ M in a calcein‐AM efflux assay using porcine kidney epithelial LLC‐PK1 and L‐MDR1 cells, overexpressing human P‐gp. Bromocriptine at 10 μ M reduced the IC 50 of doxorubicin (DXR) in K562‐DXR from 9000 to 270 ng/ml and that of vincristine (VCR) in K562‐VCR from 700 to 0.30 ng/ml, whereas the IC 50 values of DXR and VCR in the K562 subline were only marginally affected by these drugs. Bromocriptine restored the anticancer effect of DXR, VCR, vinblastine, vinorelbine and etoposide on MDR‐tumor cells overexpressing P‐gp. These observations suggest that bromocriptine has the potential to reverse tumor MDR involving the efflux protein P‐gp in the clinical situation.