Arsenic accumulation decreased in metallothionein null Cisplatin-resistant cell lines.
Metallothionein (MT) is known to play an important role in the resistance of tumor cells to cis-diamminedichloroplatinum (II) (cisplatin). To identify non-MT factors of cisplatin resistance, we characterized cisplatin-resistant cell lines derived from MT-null cells. All of the cisplatin-resistant MT- null cell lines, namely MKCr-1, -3, -4, -12, and -13, showed strong cisplatin resistance and decreased platinum accumulation. Some multidrug resistance proteins (MRPs) have been reported to contribute to cisplatin resistance. However, no significant difference of the MRPs was observed in any of these cell lines. The MKCrs showed cross-resistance to other metals such as arsenite, arsenate, cadmium and antimony. The arsenate and arsenite sensitivities were highly correlated with sensitivity to cisplatin. In addition, the degree of arsenite accumulation was correlated with the degree of cisplatin accumulation. These results suggest that the cisplatin resistance was strongly correlated with the arsenite transport mechanism in these cells.
Suzuki
Toshihiro
T
Department of Analytical Biochemistry, Meiji Pharmaceutical University, 2-522-1 Noshio, Kiyose, Tokyo 204-8588, Japan. tssuzuki@my-pharm.ac.jp
Ohata
Shigeki
S
Togawa
Tadayasu
T
Himeno
Seiichiro
S
Tanabe
Shinzo
S
D018435:ATP Binding Cassette Transporter, Subfamily B / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D000970:Antineoplastic Agents / Q000378:metabolism* / Q000494:pharmacology; D018053:Arsenites / Q000378:metabolism* / Q000494:pharmacology; D001692:Biological Transport; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000378:metabolism* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D019008:Drug Resistance, Neoplasm; D020128:Inhibitory Concentration 50; D008668:Metallothionein / Q000172:deficiency*; D051379:Mice; D012333:RNA, Messenger / Q000378:metabolism; D017670:Sodium Compounds / Q000378:metabolism* / Q000494:pharmacology