Increase in doxorubicin cytotoxicity by inhibition of P-glycoprotein activity with lomerizine.

Article Details

Citation

Copy to clipboard

Shiraki N, Hamada A, Ohmura T, Tokunaga J, Oyama N, Nakano M

Increase in doxorubicin cytotoxicity by inhibition of P-glycoprotein activity with lomerizine.

Biol Pharm Bull. 2001 May;24(5):555-7.

PubMed ID

11379779 [ View in PubMed

]

Abstract

Acquired resistance to chemotherapy is a major problem during cancer treatment. One mechanism for drug resistance is overexpression of the MDR (multidrug resistance)1 gene encoding the transmembrane efflux pump, P-glycoprotein (P-gp). Calcium channel blockers such as verapamil, nifedipine and nicardipine have been shown to reverse cellular drug resistance by inhibiting P-gp drug efflux. This study evaluated whether a new calcium channel blocker, lomerizine, influenced doxorubicin (Dox) cytotoxicity and P-gp activity in a P-gp-expressing cell line compared to a non-expressing subline. Verapamil, and even more markedly, lomerizine, increased cellular uptake of calcein transported by P-gp in a P-gp-expressing erythroleukemia cell line, K562-Dox. Ten microM of lomerizine reduced the IC50 of doxorubicin in the K562-Dox from 60000 ng/ml to 800 ng/ml, whereas the IC50 of doxorubicin in the K562 subline was only marginally affected by these drugs. Lomerizine showed greater reduction in P-gp efflux than verapamil at an equimolar concentration. These results suggest that lomerizine has the clinical potential to reverse tumor MDR involving the efflux protein P-gp.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Lomerizine	P-glycoprotein 1	Protein	Humans	Yes	Inhibitor	Details

Drug Transporters

Drug	Transporter	Kind	Organism	Pharmacological Action	Actions
Lomerizine	P-glycoprotein 1	Protein	Humans	Unknown	Inhibitor	Details