Selectivity and potency of microcystin congeners against OATP1B1 and OATP1B3 expressing cancer cells

PLoS ONE

Volumn 9, Issue 3, 2014, Pages

  Niedermeyer, Timo H J ^a,b   Daily, Abigail ^c   Swiatecka Hagenbruch, Monika ^a   Moscow, Jeffrey A ^c  

^a CYANO BIOTECH GMBH   (Germany)

^b UNIVERSITY OF TÜBINGEN   (Germany)

^c UNIVERSITY OF KENTUCKY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

MICROCYSTIN; SOLUTE CARRIER ORGANIC ANION TRANSPORTER 1B1; SOLUTE CARRIER ORGANIC ANION TRANSPORTER 1B3; CYCLOPEPTIDE; NODULARIN; ORGANIC ANION TRANSPORTER; SLCO1B1 PROTEIN, HUMAN; SLCO1B3 PROTEIN, HUMAN;

ARTICLE; CANCER CELL; CONTROLLED STUDY; CYANOBACTERIUM; DRUG CYTOTOXICITY; DRUG POTENCY; DRUG SCREENING; EXPRESSION VECTOR; IC 50; MICROCYSTIS AERUGINOSA; NODULARIA; PLANKTOTHRIX RUBESCENS; ANTAGONISTS AND INHIBITORS; CHEMISTRY; HUMAN; IC50; METABOLISM; NEOPLASM; TUMOR CELL LINE;

CELL LINE, TUMOR; HUMANS; INHIBITORY CONCENTRATION 50; MICROCYSTINS; NEOPLASMS; ORGANIC ANION TRANSPORTERS; ORGANIC ANION TRANSPORTERS, SODIUM-INDEPENDENT; PEPTIDES, CYCLIC;

EID: 84897558697     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0091476     Document Type: Article

References (95)

1. Watanabe MF, Harada K, Carmichael WW, Fujiki H (1995) Toxic Microcystis. CRC Press.
2. Dittmann E, Wiegand C (2006) Cyanobacterial toxins-occurrence, biosynthesis and impact on human affairs. Mol Nutr Food Res 50: 7-17. (Pubitemid 43155092)
3. Van Apeldoorn ME, van Egmond HP, Speijers GJ, Bakker GJI (2007) Toxins of cyanobacteria. Mol Nutr Food Res 51: 7-60. (Pubitemid 46144763)
4. Pearson L, Mihali T, Moffitt M, Kellmann R, Neilan B (2010) On the Chemistry, Toxicology and Genetics of the Cyanobacterial Toxins, Microcystin, Nodularin, Saxitoxin and Cylindrospermopsin. Mar Drugs 8: 1650-1680.
5. Goldberg J, Huang H, Kwon Y, Greengard P, Nairn AC, et al. (1995) Three-dimensional structure of the catalytic subunit of protein serine/threonine phosphatase-1. Nature 376: 745-753.
6. Taylor C, Quinn RJ, Suganuma M, Fujiki H (1996) Inhibition of protein phosphatase 2A by cyclic peptides modelled on the microcystin ring. Bioorg Med Chem Lett 6: 2113-2116. (Pubitemid 26279999)
7. Bagu JR, Sykes BD, Craig MM, Holmes CFB (1997) A Molecular Basis for Different Interactions of Marine Toxins with Protein Phosphatase-1. J Biol Chem 272: 5087-5097.
8. Gulledge BM, Aggen JB, Eng H, Sweimeh K, Chamberlin AR (2003) Microcystin Analogues Comprised Only of Adda and a Single Additional Amino Acid Retain Moderate Activity as PP1/PP2A Inhibitors. Bioorg Med Chem Lett 13: 2907-2911. (Pubitemid 37386248)
9. MacKintosh C, Beattie KA, Klumpp S, Cohen P, Codd GA (1990) Cyanobacterial microcystin-LR is a potent and specific inhibitor of protein phosphatases 1 and 2A from both mammals and higher plants. FEBS 264: 187-192. (Pubitemid 20169213)
10. Tillett D, Dittmann E, Erhard M, von Döhren H, Börner T, et al. (2000) Structural organization of microcystin biosynthesis in Microcystis aeruginosa PCC7806: an integrated peptide-polyketide synthetase system. Chem Biol 7: 753-764.
11. Christiansen G, Fastner J, Erhard M, Börner T, Dittmann E (2003) Microcystin Biosynthesis in Planktothrix: Genes, Evolution, and Manipulation. J Bacteriol 185: 564-572. (Pubitemid 36070483)
12. Hicks LM, Moffitt MC, Beer LL, Moore BS, Kelleher NL (2006) Structural characterization of in Vitro and in Vivo Intermediates on the Loading Module of Microcystin Synthetase. ACS Chem Biol 1: 93-102.
13. Botes DP, Tuinman AA, Wessels PL, Viljoen CC, Kruger H, et al. (1984) The Structure of Cyanoginosin-LA, a Cyclic Heptapeptide Toxin from the Cyanobacterium Microcystis aeruginose. J Chem Soc Perkin Trans I: 2311-2318.
14. Botes DP, Wessels PL, Kruger H, Runnegar MTC, Santikarn S, et al. (1985) Structural Studies on Cyanoginosins-LR,-YR,-YA, and-YM, Peptide Toxins from Microcystis aeruginosa. J Chem Soc Perkin Trans I 1: 2747-2748.
15. Gathercole PS, Thiel PG (1987) Liquid chromatographic determination of the cyanoginosins, toxins produced by the cyanobacterium Microcystis aeruginosa. J Chromatogr 408: 435-440. (Pubitemid 17159048)
16. Kusumi T, Ooi T, Watanabe MM, Takahasi H, Kakisawa H (1987) Cyanoviridin RR, a toxin from the cyanobacterium (blue-green alga) Microcystis viridis. Tetrahedron Lett 28: 4695-4698.
17. Krishnamurthy T, Szafraniec L, Hunt DF, Shabanowitz J, Yates III JR, et al. (1989) Structural characterization of toxic cyclic peptides from blue-green algae by tandem mass spectrometry. Proc Natl Acad Sci USA 86: 770-774.
18. Meriluoto JAO, Sandström A, Eriksson JE, Remaud G, Craig AG, et al. (1989) Structure and toxicity of a peptide hepatotoxin from the cyanobacterium Oscillatoria agardhii. Toxicon 27: 1021-1034. (Pubitemid 19226956)
19. Stoner RD, Adams WH, Slatkini DN, Siegelman HW (1989) The effects of single L-amino acid substitution on the lethal potencies of the microcystins. Toxicon 27: 825-828. (Pubitemid 19172037)
20. Harada K, Ogawa K, Matsuura K, Murata H, Suzuki M, et al. (1990) Structural Determination of Geometrical Isomers of Microcystins LR and RR from Cyanobacteria by Two-Dimensional NMR Spectroscopic Techniques. Chem Res Toxicol 3: 473-481. (Pubitemid 20342205)
21. Sivonen K, Carmichael WW, Namikoshi M, Rinehart KL, Dahlem AM, et al. (1990) Isolation and Characterization of Hepatotoxic Microcystin Homologs from the Filamentous Freshwater Cyanobacterium Nostoc sp. Strain 152. Appl Environ Microbiol 56: 2650-2657. (Pubitemid 20273093)
22. Harada K, Ogawa K, Kimura Y, Murata H, Suzuki M, et al. (1991) Microcystins from Anabaena flos-aquae NRC 525-17. Chem Res Toxicol 4: 535-540.
23. Harada K, Ogawa K, Matsuura K, Nagai H, Murata H, et al. (1991) Isolation of two toxic heptapeptide microcystins from an axenic strain of Microcystis aeruginosa, K-139. Toxicon 29: 479-489.
24. Kiviranta J, Namikoshi M, Sivonen K, Evans WR, Carmichael WW, et al. (1992) Structure determination and toxicity of a new microcystin from Microcystis aeruginosa strain 205. Toxicon 30: 1093-1098.
25. Namikoshi M, Sivonen K, Evans WR, Carmichael WW, Rouhiainen L, et al. (1992) Structures of three new homotyrosine-containing microcystins and a new homophenylalanine variant from Anabaena sp. strain 66. Chem Res Toxicol 5: 661-666.
26. Namikoshi M, Rinehart KL, Sakai R, Stotts RR, Dahlem AM, et al. (1992) Identification of 12 Hepatotoxins from a Homer Lake Bloom of the Cyanobacteria Microcystis aeruginosa, Microcystis viridis, and Microcystis wesenbergii: Nine New Microcystins. J Org Chem 57: 866-872.
27. Namikoshi M, Sivonen K, Evans WR, Carmichael WW, Sun F, et al. (1992) Two new L-serine variants of microcystins-LR and-RR from Anabaena sp. strain 202 A1 and 202 A2. Toxicon 30: 1457-1464.
28. Namikoshi M, Sivonen K, Evans WR, Sun F, Carmichael WW, et al. (1992) Isolation and structures of microcystins from a cyanobacterial water bloom (Finland). Toxicon 30: 1473-1479.
29. Sivonen K, Namikoshi TM, Evans WR, Färdig M, Carmichael WW, et al. (1992) Three New Microcystins, Cyclic Heptapeptide Hepatotoxins, from Nostoc sp. Strain 152. Chem Res Toxicol 5: 464-469.
30. Sivonen K, Namikoshi M, Evans WR, Gromov BV, Carmichael WW, et al. (1992) Isolation and structures of five microcystins from a Russian Microcystis aeruginosa strain CALU 972. Toxicon 30: 1481-1485.
31. Sivonen K, Skulberg OM, Namikoshi M, Evans WR, Carmichael WW, et al. (1992) Two methyl ester derivatives of microcystins, cyclic heptapeptide hepatotoxins, isolated from Anabaena flos-aquae strain CYA 83/1. Toxicon 30: 1465-1471.
32. Craig M, McCready TL, Luu HA, Smillie MA, Dubord P, et al. (1993) Identification and characterization of hydrophobic microcystins in canadian freshwater cyanobacteria. Toxicon 31: 1541-1549. (Pubitemid 24033181)
33. Luukkainen R, Sivonen K, Namikoshi M, Färdig M, Rinehart KL, et al. (1993) Isolation and identification of eight microcystins from thirteen Oscillatoria agardhii strains and structure of a new microcystin. Appl Environ Microbiol 59: 2204-2209. (Pubitemid 23205811)
34. Azevedo SMFO, Evans WR, Carmichael WW, Namikoshi M (1994) First report of microcystins from a Brazilian isolate of the cyanobacterium Microcystis aeruginosa. J Appl Phycol 6: 261-265. (Pubitemid 2103576)
35. Luukkainen R, Namikoshi M, Sivonen K, Rinehart KL, Niemelä SI (1994) Isolation and identification of 12 microcystins from four strains and two bloom samples of Microcystis sp.: structure of a new hepatotoxin. Toxicon 32: 133-139. (Pubitemid 24047970)
36. Bateman KP, Thibault P, Douglas DJ, White RL (1995) Mass spectral analyses of microcystins from toxic cyanobacteria using on-line chromatographic and electrophoretic separations. J Chromatogr A 712: 253-268.
37. Namikoshi M, Sun F, Choi BW, Rinehart KL, Carmichael WW, et al. (1995) Seven More Microcystins from Homer Lake Cells: Application of the General Method for Structure Assignment of Peptides Containing.alpha.,.beta.-Dehy-droamino Acid Unit(s). J Org Chem 60: 3671-3679.
38. Sano T, Kaya K (1995) A 2-Amino-2-Butenoic Acid(Dhb)-Containing Microcystin Isolated from Oscillatoria agardhii. Tetrahedron Lett 36: 8603-8606.
39. Beattie KA, Kaya K, Sano T, Codd GA (1998) Three dehydrobutyrine- containing microcystins from Nostoc. Phytochemistry 47: 1289-1292. (Pubitemid 28232514)
40. Lee TH, Chen YM, Chou HN (1998) First report of microcystins in Taiwan. Toxicon 36: 247-255.
41. Namikoshi M, Yuan M, Sivonen K, Carmichael WW, Rinehart KL, et al. (1998) Seven New Microcystins Possessing Two L-Glutamic Acid Units, Isolated from Anabaena sp. Strain 186. Chem Res Toxicol 11: 143-149. (Pubitemid 28128446)
42. Sano T, Kaya K (1998) Two New (E)-2-Amino-2-Butenoic Acid (Dhb)-Containing Microcystins Isolated from Oscillatoria agardhii. Tetrahedron 54: 463-470. (Pubitemid 28015457)
43. Sano T, Beattie KA, Codd GA, Kaya K (1998) Two (Z)-dehydrobutyrine- containing microcystins from a hepatotoxic bloom of Oscillatoria agardhii from Soulseat Loch, Scotland. J Nat Prod 61: 851-853. (Pubitemid 28317162)
44. Brittain S, Mohamed ZA, Wang J, Lehmann VKB, Carmichael WW, et al. (2000) Isolation and characterization of microcystins from a River Nile strain of Oscillatoria tenuis Agardh ex Gomont. Toxicon 38: 1759-1771. (Pubitemid 30349127)
45. Lee T-H, Chou H-N (2000) Isolation and identification of seven microcystins from a cultured M.TN-2 strain of Microcystis aeruginosa. Bot Bull Acad Sin 41: 197-202. (Pubitemid 30610248)
46. Matthiensen A, Beattie KA, Yunes JS, Kaya K, Codd GA (2000) [D-Leu1]Microcystin-LR, from the cyanobacterium Microcystis RST 9501 and from a Microcystis bloom in the Patos Lagoon estuary, Brazil. Phytochemistry 55: 383-387.
47. Robillot C, Vinh J, Puiseux-Dao S, Hennion M-C (2000) Hepatotoxin Production Kinetics of the Cyanobacterium Microcystis aeruginosa PCC 7820, as Determined by HPLC-Mass Spectrometry and Protein Phosphatase Bioassay. Environ Sci Technol 34: 3372-3378. (Pubitemid 30643758)
48. Grach-Pogrebinsky O, Sedmak B, Carmeli S (2004) Seco[D-Asp3]microcystin- RR and [D-Asp3, D-Glu(OMe)6]microcystin-RR, Two New Microcystins from a Toxic Water Bloom of the Cyanobacterium Planktothrix rubescens. J Nat Prod 67: 337-342. (Pubitemid 38410615)
49. Oksanen I, Jokela J, Fewer DP, Wahlsten M, Rikkinen J, et al. (2004) Discovery of Rare and Highly Toxic Microcystins from Lichen-Associated Cyanobacte-rium Nostoc sp. Strain IO-102-I. Appl Environ Microbiol 70: 5756-5763. (Pubitemid 39471814)
50. Sano T, Takagi H, Kaya K (2004) A Dhb-microcystin from the filamentous cyanobacterium Planktothrix rubescens. Phytochemistry 65: 2159-2162. (Pubitemid 38981672)
51. Diehnelt CW, Dugan NR, Peterman SM, Budde WL (2006) Identification of microcystin toxins from a strain of Microcystis aeruginosa by liquid chromatography introduction into a hybrid linear ion trap-Fourier transform ion cyclotron resonance mass spectrometer. Anal Chem 78: 501-512. (Pubitemid 43100383)
52. Mayumi T, Kato H, Imanishi S, Kawasaki Y, Hasegawa M, et al. (2006) Structural Characterization of Microcystins by LC/MS/MS under Ion Trap Conditions. J Antibiot 59: 710-719. (Pubitemid 46074906)
53. Christiansen G, Yoshida WY, Blom JF, Portmann C, Gademann K, et al. (2008) Isolation and Structure Determination of Two Microcystins and Sequence Comparison of the McyABC Adenylation Domains in Planktothrix Species. J Nat Prod 71: 1881-1886.
54. Del Campo FF, Ouahid Y (2010) Identification of microcystins from three collection strains of Microcystis aeruginosa. Environ Pollut 158: 2906-2914.
55. Okello W, Portmann C, Erhard M, Gademann K, Kurmayer R (2010) Occurrence of Microcystin-Producing Cyanobacteria in Ugandan Freshwater Habitats. Environ Toxicol 25: 367-380.
56. Niedermeyer THJ, Kurmayer R, Schmieder P (2014) Isolation of microcystins from the cyanobacterium Planktothrix rubescens strain No80. Nat Products Bioprospect, accepted.
57. Mazur-Marzec H, Meriluoto J, Plinski M, Szafranek J (2006) Characterization of nodularin variants in Nodularia spumigena from the Baltic Sea using liquid chromatography/mass spectrometry/mass spectrometry. Rapid Commun Mass Spectrom 20: 2023-2032. (Pubitemid 44024580)
58. Rinehart KL, Harada K, Namikoshi M, Chen C, Harvis CA, et al. (1988) Nodularin, Microcystin, and the Configuration of Adda. J Am Chem Soc 110: 8557-8558.
59. Beattie KA, Kaya K, Codd GA (2000) The cyanobacterium Nodularia PCC 7804, of freshwater origin, produces [L-Har2] nodularin. Phytochemistry 54: 57-61. (Pubitemid 30337408)
60. Namikoshi M, Choi BW, Sakai R, Sun F, Rinehart KL, et al. (1994) New Nodularins: A General Method for Structure Assignment. J Org Chem 59: 2349-2357. (Pubitemid 24193314)
61. Toivola DM, Eriksson JE (1999) Toxins Affecting Cell Signalling and Alteration of Cytoskeletal Structure. Toxicol Vitr 13: 521-530. (Pubitemid 29354172)
62. Campos A, Vasconcelos V (2010) Molecular Mechanisms of Microcystin Toxicity in Animal Cells. Int J Mol Sci 11: 268-287.
63. König J, Seithel A, Gradhand U, Fromm MF (2006) Pharmacogenomics of human OATP transporters. Naunyn Schmiedebergs Arch Pharmacol 372: 432-443.
64. Hagenbuch B, Gui C (2008) Xenobiotic transporters of the human organic anion transporting polypeptides (OATP) family. Xenobiotica 38: 778-801.
65. Kalliokoski A, Niemi M (2009) Impact of OATP transporters on pharmacoki-netics. Br J Pharmacol 158: 693-705.
66. Zurawell RW, Chen H, Burke JM, Prepas EE (2005) Hepatotoxic cyanobac-teria: a review of the biological importance of microcystins in freshwater environments. J Toxicol Environ Health Part B 8: 1-37. (Pubitemid 40066024)
67. Pegram RA, Humpage AR, Neilan BA, Runnegar MT, Nichols T, et al. (2008) Cyanotoxins Workgroup Report. Adv Exp Med Biol 619: 317-381.
68. Dawson RM (1998) The Toxicology of Microcystins. Toxicon 36: 953-962. (Pubitemid 28305389)
69. Nishiwaki-Matsushima R, Ohta T, Nishiwaki S, Suganuma M, Kohyama K, et al. (1992) Liver tumor promotion by the cyanobacterial cyclic peptide toxin microcystin-LR. J Cancer Res Clin Oncol 118: 420-424.
70. Butler N, Carlisle JC, Linville R, Washburn B (2009) Microcystins-A brief overview of their toxicity and effects, with special reference to fish, wildlife, and livestock. California Environmental Protection Agency.
71. Herfindal L, Myhren L, Kleppe R, Krakstad C, Selheim F, et al. (2011) Nostocyclopeptide-M1: A Potent, Nontoxic Inhibitor of the Hepatocyte Drug Transporters OATP1B3 and OATP1B1. Mol Pharm 8: 360-367.
72. Daily A, Monks NR, Leggas M, Moscow JA (2009) Abrogation of microcystin cytotoxicity by MAP kinase inhibitors and N-acetyl cysteine is confounded by OATP1B1 uptake activity inhibition. Toxicon 55: 827-837.
73. Sainis I, Fokas D, Vareli K, Tzakos AG, Kounnis V, et al. (2010) Cyanobacterial cyclopeptides as lead compounds to novel targeted cancer drugs. Mar Drugs 8: 629-657.
74. Buxhofer-Ausch V, Secky L, Wlcek K, Svoboda M, Kounnis V, et al. (2013) Tumor-Specific Expression of Organic Anion-Transporting Polypeptides: Transporters as Novel Targets for Cancer Therapy. J Drug Deliv 2013: 1-12.
75. Hays A, Apte U, Hagenbuch B (2013) Organic anion transporting polypeptides expressed in pancreatic cancer may serve as potential diagnostic markers and therapeutic targets for early stage adenocarcinomas. Pharm Res 30: 2260-2269.
76. Liu T, Li Q (2014) Organic anion-transporting polypeptides: a novel approach for cancer therapy. J Drug Target 22: 14-22.
77. Lee W, Belkhiri A, Lockhart AC, Merchant N, Glaeser H, et al. (2008) Overexpression of OATP1B3 Confers Apoptotic Resistance in Colon Cancer. Cancer Res 68: 10315-10323.
78. Monks NR, Liu S, Xu Y, Yu H, Bendelow AS, et al. (2007) Potent cytotoxicity of the phosphatase inhibitor microcystin LR and microcystin analogues in OATP1B1-and OATP1B3-expressing HeLa cells. Mol Cancer Ther 6: 587-598. (Pubitemid 46332461)
79. Muto M, Onogawa T, Suzuki T, Ishida T, Rikiyama T, et al. (2007) Human liver-specific organic anion transporter-2 is a potent prognostic factor for human breast carcinoma. Cancer Sci 98: 1570-1576. (Pubitemid 47308452)
80. Fischer A, Hoeger SJ, Stemmer K, Feurstein DJ, Knobeloch D, et al. (2010) The role of organic anion transporting polypeptides (OATPs/SLCOs) in the toxicity of different microcystin congeners in vitro: a comparison of primary human hepatocytes and OATP-transfected HEK293 cells. Toxicol Appl Pharmacol 245: 9-20.
81. McConnell JL, Wadzinski BE (2009) Targeting Protein Serine/Threonine Phosphatases for Drug Development. Mol Pharmacol 75: 1249-1261.
82. McCluskey A, Sim ATR, Sakoff JA (2002) Serine-Threonine Protein Phosphatase Inhibitors: Development of Potential Therapeutic Strategies. J Med Chem 45: 1151-1175. (Pubitemid 34263552)
83. Colby DA, Chamberlin AR (2006) Pharmacophore Identification: The Case of the Ser/Thr Protein Phosphatase Inhibitors. Mini-Reviews Med Chem 6: 109-120.
84. Diehnelt CW, Peterman SM, Budde WL (2005) Liquid chromatography-tandem mass spectrometry and accurate m/z measurements of cyclic peptide cyanobacteria toxins. Trends Anal Chem 24: 622-634.
85. Chen Y-M, Lee T-H, Lee S-J, Huang H-B, Huang R, et al. (2006) Comparison of protein phosphatase inhibition activities and mouse toxicities of microcystins. Toxicon 47: 742-746. (Pubitemid 43766825)
86. Blom JF, Jüttner F (2005) High crustacean toxicity of microcystin congeners does not correlate with high protein phosphatase inhibitory activity. Toxicon 46: 465-470. (Pubitemid 41218741)
87. An J, Carmichael WW (1994) Use of a Colorimetric Protein Phosphatase Inhibition Assay and Enzyme Linked Immunosorbent Assay for the Study of Microcystins and Nodularins. Toxicon 32: 1495-1507.
88. Andersen R (2005) Algal Culturing Techniques. 1st ed. Elsevier Academic Press.
89. Harada K (2004) Production of Secondary Metabolites by Freshwater Cyanobacteria. Chem Pharm Bull (Tokyo) 52: 889-899. (Pubitemid 41701862)
90. Piantini U, Sorensen OW, Ernst RR (1982) Multiple quantum filters for elucidating NMR coupling networks. J Am Chem Soc 104: 6800-6801.
91. Niedermeyer THJ, Strohalm M (2012) mMass as a software tool for the annotation of cyclic peptide tandem mass spectra. PLoS One 7: e44913.
92. Boaru DA, Dragoş N, Schirmer K (2006) Microcystin-LR induced cellular effects in mammalian and fish primary hepatocyte cultures and cell lines: A comparative study. Toxicology 218: 134-148. (Pubitemid 41821345)
93. Tsakalozou E, Adane ED, Kuo K-L, Daily A, Moscow JA, et al. (2013) The Effect of Breast Cancer Resistance Protein, Multidrug Resistant Protein 1, and Organic Anion-Transporting Polypeptide 1B3 on the Antitumor Efficacy of the Lipophilic Camptothecin 7-t-Butyldimethylsilyl-10-Hydroxycamptothecin (AR-67) In Vitro. Drug Metab Dispos 41: 1404-1413.
94. Moscow JA, Connolly T, Myers TG, Cheng CC, Paull K, et al. (1997) Reduced Folate Carrier Gene (RFC1) Expression and Anti-Folate Resistance in Transfected and Non-Selected Cell Lines. Int J Cancer 72: 184-190. (Pubitemid 27314657)
95. Moscow JA, Swanson CA, Cowan KH (1993) Decreased melphalan accumulation in a human breast cancer cell line selected for resistance to melphalan. Br J Cancer 68: 732-737. (Pubitemid 23301278).