Does any relationship exist between P-glycoprotein-mediated multidrug resistance and intracellular calcium homeostasis

Abstract

Multidrug resistance (MDR) of neoplastic tissue represents a real obstacle to the effective chemotherapy of cancer. Several mechanisms of MDR were identified, from which the over-expression and efflux activity of P-glycoprotein (P-gp) - a plasma membrane ATPase (ABCB1 member of ABC transporter family) - represents the most commonly observed reason for neoplastic disease chemotherapy malfunction. The process of P-gp-mediated MDR seems to be related to intracellular calcium homeostasis, at least indirectly, for the following reasons: i. substances blocking calcium influx through L-type of calcium channels like verapamil were often found to antagonize P-gp-mediated MDR; ii. calcium signal abnormalities were observed in cells over-expressing P-gp; iii. cells with P-gp-mediated MDR were often resistant to thapsigargin; iv. several differences in intracellular calcium localization were observed when P-gp-negative and P-gp-positive cells were compared; and v. differences in the contents of several proteins of the endoplasmic reticulum involved in calcium homeostasis were observed to be associated with P-gp over-expression. This current study represents an attempt to summarize the knowledge about the possible relationship between P-gp-mediated MRD and intracellular calcium homeostasis.