Involvement of P-gp in the process of apoptosis in peripheral blood mononuclear cells

Multidrug resistance mediated by the drug-efflux protein P (P-gp) is one of mechanisms that cells use to escape death induced by drugs and other agents. The aim of the study was to evaluate the effect of P-gp inhibition on apoptosis of PHA-activated peripheral blood mononuclear cells (MNC) as well as apoptosis induced by methotrexate (MTX), dexamethasone (DEX), methylprednisolone (MP) and cortisone (COR). Apoptosis was quantified by flow cytometry using Annexin V/PI and terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling (TUNEL). P-gp expression was inhibited using verapamil (VER) and P-gp specific monoclonal antibodies (mAb). VER and mAb enhanced the apoptosis of PHA-activated MNC. Moreover these agents significantly increased the apoptosis induced by MTX, DEX, MP and COR. The results of this study suggest that P-gp is involved in the process of apoptosis in peripheral blood mononuclear cells.