Skip to main content
SpringerLink
Log in

Non-P-glycoprotein multidrug resistance in cell lines which are defective in the cellular accumulation of drug

  • Published:
Cytotechnology Aims and scope Submit manuscript

Abstract

Non-Pgp mdr related to a defect in drug accumulation has now been documented in a number of different cell lines exposed to certain cytotoxic agents. In studies conducted thus far most isolates have been obtained after selection in either adriamycin or mitoxantrone. The work in this area is in its early stages and very little is known about the molecular events which contribute to this mode of drug resistance. At the present time no protein with drug binding properties comparable to Pgp has been identified in non-Pgp mdr isolates. Evidence based on the finding that all isolates do not respond in the same way to reversal agents such as verapamil suggests the possibility that more than one mechanism may exist for non-Pgp mdr. Future studies may thus reveal that cells contain a multiplicity of genes which upon transcriptional activation can function to alter drug transport processes and thus contribute to the development of mdr. Identifying and characterizing these genes will be important since they may function in transport systems of normal cells. The exact identity of proteins which contribute to non-Pgp mdr remains to be determined. One protein designated P190 has been found to be overexpressed in cell lines of human promyelocytic leukemia, lung and adenocarcinoma treated with adriamycin. The protein also is increased in some clinical samples from patients undergoing chemotherapy. P190 which has a minor sequence homology with Pgp can bind ATP and may thus contribute to the energy dependent drug efflux systems found in cells containing this protein. Transfection studies with p P190 cDNA should determine whether this protein actually contributes to drug resistance. Many other protein changes have been detected in non-Pgp mdr cells but the importance of these in resistance also remains to be determined. In some systems a particular protein change can be identified in multiple independent isolates suggesting a correlation between the development of resistance and the presence of this cellular alteration.

Experiments conducted thus far on the mechanism of non-Pgp mdr are intriguing. Studies utilizing fluorescence microscopy to follow the fate of daunomycin suggests that the drug passes to the interior of the cell and eventually localizes in the Golgi apparatus. Drug located at this site may move directly into an efflux pathway for rapid extrusion from the cell. Evidence also indicates that as drug leaves the Golgi some may be sequestered into other organelles such as lysosomes or mitochondria. Sequestration may thus be another means of protecting the cell from the cytotoxic action of the drug. Very little is known of the molecular details of these events and some new technological approaches may be required to gain insight into efflux and sequestration pathways.In vitro systems for drug transport would certainly be important in these studies.

A major question to be answered in the future is whether non-Pgp mdr actually contributes to clinical drug resistance. This will certainly be clarified as new probes which can selectively detect this type of resistance are developed. Some studies have shown that in experimental isolates a low level non-Pgp mdr can precede a Pgp mdr which appears after continuous treatment of cells with drug. Possibly these findings have clinical relevance.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

Abbreviations

PM:

plasma membranes

ER:

endoplasmic reticulum

TPA:

12-0-tetradecanoylphorbol-13-acetate

DMSO:

dimethyl sulfoxide

RA:

retinoic acid

VP-16:

4′-deimethylepipodophyllotoxin-9-(4,6-0-ethylidene)-β-D-glucopyranoside

MRP:

Multidrug-resistance associated protein

IC50 :

Amount of drug required to inhibit cellular growth b6 50%

NBD:

7-chloro-4-nitrobenz-2-oxa 1,3-diazole

Pgp:

P-glycoprotein

mdr:

multidrug resistance

EGF:

epidermal growth factor

References

  • Aquino A, Hartman KD, Kvode MC, Grant S, Huang K-P, Niu C-H and Glazer RI (1988) Role of protein kinase C in phosphorylation of vinculin in adriamycin-resistant HL60 leukemia cells. Cancer Res 48: 3324–3329.

    Google Scholar 

  • Aquino A, Warren B, Omichinski J, Hartman KD and Glazer RI (1990a) Protein kinase Cγ is present in adriamycin-resistant HL60 leukemia cells. Biochem Biophys Res Commun 166: 723–728.

    Google Scholar 

  • Aquino A, Johnson-Thompson M and Glazer RI (1990b) Enhanced Ca2+-dependent proteolysis associated with adriamycin resistant HL60 cells. Oncology Res 2: 243–247.

    Google Scholar 

  • Baas F, Jongsma APM, Broxterman HJ, Arceci RJ, Housman D, Scheffer GL, Riethorst A, van Groenigen M, Nieuwint AWM and Joenje H (1990) Non-P-glycoprotein mediated mechanism for multidrug resistance precedes P-glycoprotein expression duringin vitro selection for doxorubicin resistance in a human lung cancer cell line. Cancer Res 50: 5392–5398.

    Google Scholar 

  • Baker RM, Chen Y, Richard B, Fredericks WJ, Cason E, Karakousis C, Center M, Slocum HK and Rustum Y (1993) Relation of multidrug resistance markers assessed by immunoblotting to clinical course for disease in adult sarcoma. Proc Am Assoc Cancer Res 34: 232.

    Google Scholar 

  • Barrand MA, Tsuruo T and Twentyman PR (1990) Differences between monoclonal antibodies in immunohistochemical detection of P-glycoprotein in human and mouse multidrug resistant cell lines. Br J Cancer 62: 510–514.

    Google Scholar 

  • Barrand MA, Broxterman HJ, Wright KA, Rhodes T and Twentyman PR (1992) Immunodetection of a 190 kd protein in non-P-glycoprotein containing mdr cells derived from small cell and non-small cell lung tumours. Br J Cancer 65(suppl XVI): 21.

    Google Scholar 

  • Barrand MA, Rhodes T, Center MS and Twentyman PR (1993) Chemosensitisation and drug accumulation effects of cyclosporin A, PSC-833 and verapamil in human mdr large cell lung cancer cells expressing a 190k membrane protein distinct from P-glycoprotein. Eur J Cancer 29: 408–415.

    Google Scholar 

  • Bhalla K, Hindenburg A, Taub RN and Grant S (1985) Isolation and characterization of an anthracycline-resistant human leukemic cell line. Cancer Res 45: 3657–3662.

    Google Scholar 

  • Biedler JL and Riehm H (1970) Cellular resistance to actinomycin D in Chinese hamster cellsin vitro: crossresistance, radioautographic and cytogenetic studies. Cancer Res 30: 1174–1184.

    Google Scholar 

  • Borellini F, Aquino A, Josephs SF and Glazer RI (1990) Increased expression and DNA binding activity of transcription factor Spl in doxorubicin resistant HL60 leukemia cells. Molec Cell Biol 10: 5541–5547.

    Google Scholar 

  • Bowman EJ, Siebers A and Altendorf K (1988) Bafilomycins: A class of inhibitors of membrane ATPase from microorganisms, animal cells, and plant cells. Proc Natl Acad Sci USA 85: 7972–7976.

    Google Scholar 

  • Callen DF, Baker E, Simmers RN, Seshadri R and Roninson IB (1987) Localization of the human multidrug resistance gene, Mdr1 to 7q21.1. Human Genet 77: 142–144.

    Google Scholar 

  • Cass CE, Janowska-Wieczorek A, Lynch MA, Sheinin H, Hindenburg AA and Beck WT (1989) Effect of duration of exposure to verapamil on vincristine activity against multidrug-resistant human leukemic cell lines. Cancer Res 49: 5798–5804.

    Google Scholar 

  • Chen C-J, Chin JE, Ueda K, Clark DP, Pastan I, Gottesman MM and Roninson IB (1986) Internal duplication and homology with bacterial transport proteins in the mdr1 (P-glycoprotein) gene from multidrug-resistant human cells. Cell 47:381–389.

    Google Scholar 

  • Cole SPC, Chanda ER, Dicke FP, Gerlach JH and Mirski SEL (1991) Non-P-glycoprotein-mediated multidrug resistance in a small cell lung cancer cell line: evidence for decreased susceptibility to drug-induced DNA damage and reduced levels of topoisomerase II. Cancer Res 51:3345–3352.

    Google Scholar 

  • Cole SPC, Bhardwaj G, Gerlach JH, Mackie JE, Grant CE, Almquist KC, Stewart AJ, Kurz EU, Duncan AMV and Deeley RG (1992) Overexpression of a transporter gene in a multidrug-resistant human lung cancer cell line. Science 258: 1650–1654.

    Google Scholar 

  • Cole SPC and Deeley RG (1993) Multidrug resistance associated protein: sequence correction. Science 260:879.

    Google Scholar 

  • Coley HM, Workman P and Twentyman PR (1991) Retention of activity by selected anthracyclines in a multidrug resistant human large cell lung carcinoma line without P-glycoprotein hyperexpression. Br J Cancer 63: 351–357.

    Google Scholar 

  • Cornwall MM, Tsuruo T, Gottesman MM and Pastan I (1987) ATP binding properties of P-glycoprotein from multi-drug resistant KB cells. FASEB J 1: 51–54.

    Google Scholar 

  • Dalton WS, Cress AE, Alberts DS and Trent JM (1988) Cytogenetic and phenotypic analysis of a human colon carcinoma cell line resistant to mitoxantrone. Cancer Res 48: 1882–1888.

    Google Scholar 

  • Danø K (1973) Active outward transport of daunomycin in resistant Ehrlich Ascite tumor cells. Biochim Biophys Acta 324: 466–483.

    Google Scholar 

  • de Lange JHM, Schipper NW, Schuurhuis GJ, ten Kate TK, van Heijningen ThHM, Pinedo HM, Lankelma J and Baak JPA (1992) Quantification by laser scan microscopy of intracellular doxorubicin distribution. Cytometry 13: 571–576.

    Google Scholar 

  • Eijdems EWHM, Borst P, Jongsma APM, de Jong S, de Vries, EGE, van Groenigen M, Versantvoort CHM, Nieuwint AWH and Baas F (1992) Genetic transfer of non-P-glycoproteinmediated multidrug resistance (MDR) in somatic cell fusion: dissection of a compound MDR phenotype. Proc Natl Acad Sci USA 89: 3498–3502.

    Google Scholar 

  • Endicott JA and Ling V (1989) The biochemistry of P-glycoprotein-mediated multidrug resistance. Ann Rev Biochem 58: 137–171.

    Google Scholar 

  • Ferguson RJ, Fisher MH, Stephenson J, Li D-h, Zhou B-S and Cheng Y-C (1988) Combined modalities of resistance in etoposide-resistant human KB cell lines. Cancer Res 48: 5956–5964.

    Google Scholar 

  • Fugiwara T, Oda K, Yokata S, Takatsuki A and Ikehara Y (1988) Brefeldin A causes disassembly of the Golgi complex and accumulation of secretory proteins in the endoplasmic reticulum. J Biol Chem 263: 18545–18552.

    Google Scholar 

  • Gervasoni JE Jr, Taub RN, Rosado M, Krishna S, Stewart VJ, Knowles DM, Bhalla K, Ross DD, Baker MA, Lutzky J and Hindenburg AA (1991) Membrane glycoprotein changes associated with anthracycline resistance in HL60 cells. Cancer Chemother Pharmacol 28: 93–101.

    Google Scholar 

  • Gervasoni JE Jr, Fields SZ, Krishna S, Baker MA, Rosado M, Thuraisamy K, Hindenburg AA and Taub RN (1991) Subcellular distribution of daunorubicin in P-glycoprotein-positive and-negative drug-resistant cell lines using laser-assisted confocal microscopy. Cancer Res 51: 4955–4963.

    Google Scholar 

  • Gervasoni JE Jr, Taub RN, Yu MT, Warburton D, Sabbath M, Gill S, Coppock DL, D'Alessandri J, Krishna S, Rosado M, Baker MA, Lutzky J, Chandra ER, Gerlach JH, Pinkoski MJ, Cole SPC and Hindenburg AA (1992) Homogeneous staining region in anthracycline-resistant HL60/AR cells not associated with mdr1 application. Cancer Res 52: 1–6.

    Google Scholar 

  • Goldstein LJ, Galski H, Fojo A, Willingham M, Lai S-L, Gazdar A, Pirker R, Green A, Crist W, Brodeur GM, Lieber M, Cossman J, Gottesman MM and Pastan I (1989) Expression of a multidrug resistance gene in human cancers. J Natl Cancer Inst 81: 116–124.

    Google Scholar 

  • Gros P, Croop J and Housman D (1986) Mammalian multidrug resistance gene: complete cDNA sequence indicates strong homology to bacterial transport proteins. Cell 47: 371–380.

    Google Scholar 

  • Gruber A, Vitols S, Norgren S, Areström I, Peterson C, Björkholm M, Reizenstein P and Luthman H (1992) Quantitative determination of mdr1 gene expression in leukemic cells from patients with acute leukemia. Br J Cancer 66: 266–272.

    Google Scholar 

  • Haber M, Norris MD, Kavallaris M, Bell DR, Davey PA, White L and Stewart BW (1989) Atypical multidrug resistance in a therapy-induced drug resistant human leukemia cell line (LALW-2): resistance to vinca alkaloids independent of P-glycoprotein. Cancer Res 49: 5281–5287.

    Google Scholar 

  • Hamada H and Tsuruo T (1988) Purification of the 170- to 180-kilodalton membrane glycoprotein associated with multidrug resistance. J Biol Chem 263: 1454–1458.

    Google Scholar 

  • Harker WG, Slade DL, Dalton WS, Meltzer PS and Trent JM (1989) Multidrug resistance in Mitoxantrone-selected HL60 leukemia cells in the absence of P-glycoprotein overexpression. Cancer Res 49:4542–4549.

    Google Scholar 

  • Hindenburg AA, Baker MA, Gleyzer E, Stewart VJ, Case N and Taub RN (1987) Effect of verapamil and other agents on the distribution of anthracyclines and on reversal of drug resistance. Cancer Res 47: 1421–1425.

    Google Scholar 

  • Hindenburg AA, Gervasoni JE, Krishna S, Stewart VJ, Rosado M, Lutzky J, Bhalla K, Baker MA and Taub RN (1989) Intracellular distribution and pharmokinetics of daunorubicin in anthracycline-sensitive and resistant HL60 cells. Cancer Res 49: 4607–4614.

    Google Scholar 

  • Kartner H, Evernden-Porelle D, Bradley G and Ling V (1985) Detection of P-glycoprotein in multidrug resistant cell lines by monoclonal antibodies. Nature (Lond) 316: 820–823.

    Google Scholar 

  • Keizer HG, Schuurhuis GJ, Broxterman HJ, Lankelma J, Schoonen WGEJ, van Rijn J, Pinedo HM and Joenje H (1989) Correlation of multidrug resistance with decreased drug accumulation, altered subcellular drug distribution, and increased P-glycoprotein expression in cultured SW-1573 human lung tumor cells. Cancer Res 49: 2988–2993.

    Google Scholar 

  • Kessel D and Wilberding C (1984) Mode of action of calcium antagonists which alter anthracycline resistance. Biochem Pharmacol 33: 1157–1160.

    Google Scholar 

  • Klohs WD and Steinkampf RW (1988) Possible link between the intrinsic drug resistance of colon tumors and a detoxification mechanism of intestinal cells. Cancer Res 48: 3025–3030.

    Google Scholar 

  • Klohs WD, and Steinkampf RW (1988) The effect of lysosomotropic agents and secretory inhibitors on anthracycline retention and activity in multiple drug-resistant cells. Mol Pharmacol 34: 180–185.

    Google Scholar 

  • Krishnamachary N and Center MS (1992) Detection and characterization of membrane protein changes in multidrug resistant HL60 cells. Oncol Res 4: 23–28.

    Google Scholar 

  • Li M, Latoud C and Center MS (1991) Cloning and sequencing a cDNA encoding human ribosomal protein S25. Gene 107: 329–333.

    Google Scholar 

  • Li M and Center MS (1992) Regulation of ribosomal protein S25 in HL60 cells isolated for resistance to adriamycin. FEBS 298: 142–144.

    Google Scholar 

  • Ling V and Thompson LH (1974) Reduced permeability in CHO cells as a mechanism of resistance to colchicine. J Cell Physiol 83: 103–116.

    Google Scholar 

  • Lutzky J, Astor MB, Taub RN, Baker MA, Bhalla K, Gervasoni JE, Rosado M, Stewart V, Krishna S and Hindenburg AA (1989) Role of glutathione and dependent enzymes in anthracycline-resistant HL60/AR cells. Cancer Res 49: 4120–4125.

    Google Scholar 

  • Ma L and Center MS (1992) The gene encoding vacuolar H+-ATPase subunit C is overexpressed in multidrug resistant HL60 cells. Biochem Biophys Res Commun 182: 675–681.

    Google Scholar 

  • Marquardt D, McCrone S and Center MS (1990) Mechanisms of multidrug resistance in HL60 cells: detection of resistance-associated proteins with antibodies against synthetic peptides that correspond to the deduced sequence of P-glycoprotein. Cancer Res 50: 1426–1430.

    Google Scholar 

  • Marquardt D and Center MS (1991) Involvement of vacuolar H+-Adenosine triphosphatase activity in multidrug resistance in HL60 cells. J Natl Cancer Inst 83: 1098–1102.

    Google Scholar 

  • Marquardt D and Center MS (1992) Drug transport mechanisms in HL60 cells isolated for resistance to adriamycin: evidence for nuclear drug accumulation and redistribution in resistant cells. Cancer Res 52: 3157–3163.

    Google Scholar 

  • Marsh W, Sicheri D and Center MS (1986) Isolation and characterization of adriamycin-resistant HL60 cells which are not defective in the initial intracellular accumulation of drug. Cancer Res 46: 4053–4057.

    Google Scholar 

  • Marsh W and Center MS (1986) Dimethylsulfoxide, retinoic acid and 12-0-tetradecanoylphorbol-13-acetate induce a selective decrease in the phosphorylation of P150, a surface membrane phosphoprotein of HL60 cells resistant to adriamycin. Biochem Biophys Res Commun 138: 9–16.

    Google Scholar 

  • Marsh W and Center MS (1987) Adriamycin resistance in HL60 cells and accompanying modification of a surface membrane protein contained in drug-sensitive cells. Cancer Res 47: 5080–5086.

    Google Scholar 

  • McGrath T and Center MS (1987) Adriamycin resistance in the absence of detectable P-glycoprotein. Biochem Biophys Res Commun 145: 1171–1176.

    Google Scholar 

  • McGrath T and Center MS (1988) Mechanisms of multidrug resistance in HL60 cells: evidence that a surface membrane protein distinct from P-glycoprotein contributes to reduced cellular accumulation of drug. Cancer Res 48: 3959–3963.

    Google Scholar 

  • McGrath T, Latoud C, Arnold ST, Safa AR, Felsted RL and Center MS (1989) Mechanisms of multidrug resistance in proteins and levels of mdr gene expression. Biochem Pharmacol 38: 3611–3619.

    Google Scholar 

  • Mirski SEL, Gerlach JH and Cole SPC (1987) Multidrug resistance in a human small cell lung cancer cell line selected in Adriamycin. Cancer Res 47: 2594–2598.

    Google Scholar 

  • Nakagawa M, Schneider E, Dixon KH, Horton J, Kelley K, Morrow C and Cowan KH (1992) Reduced intracellular drug accumulation in the absence of P-glycoprotein (mdr1) overexpression in mitoxantrone-resistant human MCF-7 breast cancer cells. Cancer Res 52: 6175–6181.

    Google Scholar 

  • Nelson N (1989) Structure, molecular genetics, and evolution of vacuolar H+-ATPases. J Bioenerg Biomembr 21: 553–571.

    Google Scholar 

  • Nelson H, Mandiyan S, Noumi T, Moriyama Y, Miedel MC and Nelson N (1990) Molecular cloning of cDNA encoding the C subunit of H+-ATPase from bovine chromaffin granules. J Biol Chem 265: 20390–20393.

    Google Scholar 

  • Nielsen D and Skovsgaard T (1992) P-glycoprotein as multidrug transporter: a critical review of current multidrug resistant cell lines (1992) Biochim Biophys Acta 1139: 169–183.

    Google Scholar 

  • Nieuwint AWM, Baas F, Wiegant J and Joenje H (1992) Cytogenetic alterations associated with P-glycoprotein- and non-P-glycoprotein-mediated multidrug resistance in SW-1573 human lung tumor cell lines. Cancer Res 52: 4361–4371.

    Google Scholar 

  • Ragano RE and Sleight R (1985) Defining lipid transport pathways in animal cells. Science (Washington DC) 229: 1051–1057.

    Google Scholar 

  • Peterson RHF, O'Neil JA and Biedler JL. (1974) Some biochemical properties of Chinese hamster cells sensitive and resistant to actinomycin D. J Cell Biol 63: 223–779.

    Google Scholar 

  • Reeve JG, Rabbits PH and Twentyman PR (1990) Non-P-glycoprotein-mediated multidrug resistance with reduced EGF receptor expression in a human large cell lung cancer cell line. Br J Cancer 61: 851–855.

    Google Scholar 

  • Rustan AC, Nossen JØ, Tefre T and Drevon CA (1987) Inhibition of very-low-density lipoprotein secretion by chloroquine, verapamil and monensin takes place in the Golgi complex. Biochim Biophys Acta 930: 311–319.

    Google Scholar 

  • Safa AR, Glover CJ, Meyers MB, Biedler JL and Felsted RL (1986) Vinblastine photoaffinity labeling of a high molecular weight surface membrane glycoprotein specific for multidrug-resistant cells. J Biol Chem 261: 6137–6140.

    Google Scholar 

  • Safa AR, Glover CJ, Sewell JL, Meyers MB, Biedler JL and Felsted RL (1987) Identification of the multidrug resistance-related membrane glycoprotein as an acceptor for calcium channel blockers. J Biol Chem 262: 7884–7888.

    Google Scholar 

  • Safa AR (1988) Photoaffinity labeling of multidrug-resistance-related P-glycoprotein with photoactive analysis of verapamil. Proc Natl Acad Sci USA 85: 7187–7191.

    Google Scholar 

  • Scheper RJ, Bulte JWM, Brakkee JGP, Quak JJ, van der Schoot E, Balm AJM, Meijer CJLM, Broxterman HJ, Kuper CM, Lankelma J and Pinedo HM (1988) Monoclonal antibody JSB-1 detects a highly conserved epitope on the P-glycoprotein associated with multidrug resistance. Int J Cancer 42: 389–394.

    Google Scholar 

  • Schuurhuis GJ, Broxterman HJ, de Lange JHM, Pinedo HH, van Heijningen THM, Kuiper CM, Scheffer GL, Scheper RJ, van Kalken CK, Baak JPA and Lankelma J (1991) Early multidrug resistance defined by changes in intracellular doxorubicin distribution, independent of P-glycoprotein. Br J Cancer 64: 857–861.

    Google Scholar 

  • Sehested M, Skovsgaard T, and Roed H (1988) The carboxylic ionophore monensin inhibits active drug efflux and modulatesin vitro resistance in daunorubicin resistant Ehrlich ascites tumor cells. Biochem Pharmacol 37: 3305–3310.

    Google Scholar 

  • Shen D-W, Lu Y-G, Chin K-V, Pastan I and Gottesman MM (1991) Human hepatocellular carcinoma cell lines exhibit multidrug resistance unrelated to mdr1 gene expression. J Cell Sci 98: 317–322.

    Google Scholar 

  • Shinn-Liang L, Goldstein LJ, Gottesman MM, Pastan I, Chun-Ming T, Johnson BE, Mulshine JL, Ihde DC, Kayser K and Gazdar AF (1989) Mdr1 gene expression in lung cancer. J Natl Cancer Inst 81: 1144–1150.

    Google Scholar 

  • Skovsgaard T (1978) Mechanism of cross-resistance between vincristine and daunorubicin in Ehrlich ascites tumor cells. Biochem Pharmacol 27: 1221–1227.

    Google Scholar 

  • Slapak CA, Daniel JC and Levy SB (1990) Sequential emergence of distinct resistance phenotypes in murine erythroleukemic cells under adriamycin selection: decreased anthracycline uptake precedes increased P-glycoprotein expression. Cancer Res 50: 7895–7901.

    Google Scholar 

  • Slovak ML, Hoeltge GA, Dalton WS and Trent JM (1988) Pharmacological and biological evidence for differing mechanisms of doxorubicin resistance in two human cell lines. Cancer Res 48: 2793–2797.

    Google Scholar 

  • Tartakoff AM and Vassalli P (1978) Comparative studies of intercellular transport of secretory proteins. J Cell Biol 79: 694–707.

    Google Scholar 

  • Tartakoff AM (1983) Perturbation of vesicular traffic with the carboxylic ionophore monensin. Cell 32: 1026–1028.

    Google Scholar 

  • Taylor CW, Dalton WS, Parrish PR, Gleason MC, Bellamy WT, Thompson FH, Roe DJ and Trent JM (1991) Different mechanisms of decreased drug accumulation in doxorubicin and mitoxantrone resistant variants of the MCF-7 human breast cancer cell line. Br J Cancer 63: 923–929.

    Google Scholar 

  • Trent JM and Witlcowski CM (1987) Clarification of the chromosomal assignment of the human P-glycoprotein/mdr1 gene possible coincidence with the cystic fibrosis and c-met oncogene. Cancer Genet Cytogenet 26: 187–190.

    Google Scholar 

  • Tsuruo T, Lida H, Tsukagoshi S and Sakurai Y (1981) Overcoming of vincristine resistance in P388 leukemiain vivo andin vitro through enhanced cytotoxicity of vincristine and vinblastine by verapamil. Cancer Res 41: 1967–1972.

    Google Scholar 

  • Twentyman PR, Fox NE, Wright KA and Bleehen NM (1986) Derivation and preliminary characterization of adriamycin resistant lines of human lung cancer cells. Br J Cancer 53: 529–537.

    Google Scholar 

  • Versantvoort CHM, Broxterman HJ, Pinedo HM, de Vries EGE, Feller N, Kuiper CM and Lankelma J (1992) Energy-dependent processes involved in reduced drug accumulation in multidrug-resistant human lung cancer cell lines without P-glycoprotein expression. Cancer Res 52: 17–23.

    Google Scholar 

  • Volm M, Mattern J, Efferth T and Pommerenke EW (1992) Expression of several resistance mechanisms in untreated human kidney and lung carcinomas. Anticancer Res 12: 1063–1068.

    Google Scholar 

  • Wang S-Y, Moriyama Y, Mandel M, Hulmes JD, Pan Y-CE, Danho W, Nelson H and Nelson N (1988) Cloning of cDNA encoding a 32-kDa protein: an accessory polypeptide of the H+-ATPase from chromaffin granules. J Biol Chem 263: 17638–17642.

    Google Scholar 

  • Weber JB, Sircar S, Horwath J and Dion P (1989) Non-P-glycoprotein-mediated multidrug resistance in detransformed rat cells selected for resistance to methylglyoxal bis(quanylhydrazone). Cancer Res 49: 5779–5783.

    Google Scholar 

  • Yoshimori T, Yamamoto A, Moriyama Y, Futai M and Tashiro Y (1991) Bafilomycin A1, a specific inhibitor of vacuolar-type H+-ATPase, inhibits acidification and protein degradation in lysosomes of cultured cells. J Biol Chem 26: 17707–17712.

    Google Scholar 

  • Zijlstra JG, de Vries EGE and Mulder NH (1987) Multifactorial drug resistance in an adriamycin-resistant human small cell lung carcinoma cell line. Cancer Res 47: 1780–1784.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Biology, Kansas State University, 66506, Manhattan, Kansas, USA

    Melvin S. Center

Authors
  1. Melvin S. Center
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Center, M.S. Non-P-glycoprotein multidrug resistance in cell lines which are defective in the cellular accumulation of drug. Cytotechnology 12, 109–125 (1993). https://doi.org/10.1007/BF00744660

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00744660

Key words

Search

Navigation