Altered MRP is associated with multidrug resistance and reduced drug accumulation in human SW-1573 cells

Low-level doxorubicin resistance in P-glycoprotein-negative human pancreatic tumour PSN1/ADR cells implicates a brefeldin A-sensitive mechanism of drug extrusion

“…Therefore, our data suggest that the BFA/fluoroaluminate-sensitive mechanism of DOX extrusion plays a role in low-level DOX resistance associated with the MRP transporter, but may be attenuated in highly resistant clones possessing the more efficient P-gp efflux pump. A prevalent role of MRP over P-gp in early steps of MDR acquisition emerged in recent literature (Eijdems et al, 1995). Another early MDR marker found in P-gp-negative MDR clones seems to be LRP (Scheper et al, 1993), which we observed already in PSN1/ADR7.3 cells selected in 17-51 nM DOX.…”

“…Recently, new mediators of MDR were identified in P-gp-negative tumour cells resistant to doxorubicin (DOX), indicating differential mechanisms of drug extrusion. The 190 kDa multidrug resistance-associated protein (MRP), a novel member of the ABC transporters, appears to precede P-gp activation or to function solely in MDR clones (Cole et al, 1992;Flens et al, 1994;Eijdems et al, 1995). The MRP and P-gp efflux pumps confer a similar MDR phenotype (Cole et al, 1994), whereas the 190 kDa transporter seems to possess a reduced substrate specificity for the fluorescent dye rhodamine 123 and the competitive inhibitor verapamil (McGrath et al, 1989;Barrand et al, 1993).…”

Characterization of a clonal human colon adenocarcinoma line intrinsically resistant to doxorubicin

“…Vaults have been described as ribonucleoprotein particles, the majority of which can be found in the cytoplasm, while a small fraction are localized to the nuclear membrane where they are hypothesized to interact with or be part of the nuclear pore complex (Rome et al, 1991). The observed subcellular distribution suggests that they may be implicated in the bidirectional transport of a variety of substrates and/or their cytoplasmic redistribution and highlights a possible role of these organelles in mediating drug resistance (Izquierdo et al, 1996) (1992) in the small-cell lung carcinoma (SCLC) cell line H69 and since then has been described in a number of multidrug-resistant, non-P-gp-expressing cell lines (Krishnamachary and Center, 1993;Schneider et al, 1994;Eijdems et al, 1995;Versantvoort et al, 1995a). The range of chemotherapeutic drugs involved in MRP-mediated multidrug resistance broadly overlaps that observed for P-gp, including anthracyclines, epipodophyllotoxins and Vinca alkaloids (Grant et al, 1994;Zaman et al, 1994).…”

“…The range of chemotherapeutic drugs involved in MRP-mediated multidrug resistance broadly overlaps that observed for P-gp, including anthracyclines, epipodophyllotoxins and Vinca alkaloids (Grant et al, 1994;Zaman et al, 1994). The degree of resistance observed in MRPexpressing cells is generally lower than in cells overexpressing P-gp (Eijdems et al, 1995). In DOX-resistant HL-60 cells, a non-P-gp-expressing human promyelocytic leukaemia cell line, MRP was identified primarily in the endoplasmic reticulum, with lower levels also present in the plasma membrane (Marquardt and Center, 1992;Krishnamachary and Center, 1993), whereas a predominant function as a plasma membrane efflux pump has been demonstrated in a SCLC and in a non-small-cell lung carcinoma (NSCLC) cell line selected by exposure to DOX (Zaman et al, 1994 76(1), [67][68][69][70][71][72][73][74][75][76] In the present study, an additional possible mechanism for the intrinsically resistant phenotype of LoVo/C7 cells has been examined, namely alterations of PKC isoform pattern.…”

Intrinsic chemotherapy resistance to the tubulin‐binding antimitotic agents in renal cell carcinoma

“…35 The activity of MRP may also be regulated at the posttranslational level. 36 The relevance of these in vitro functional correlates of protein expression with drug resistance mechanisms in vivo in RCC is far from clear. The constitutive expression of many transport molecules by proximal tubules may confer an inherent drug resistance without the need for upregulation of expression as part of the malignant transformation process.…”