Binding of cis-dichlorodiammine platinum(II) to metallothionein in Ehrlich cells.
The antitumor agent, cis-dichlorodiammine Pt(II), is cytotoxic to Ehrlich cells in culture. These cells contain a substantial amount of metallothionein in the absence of inducers of the protein. At concentrations of drug which cause 60% inhibition of cell proliferation, most of the platinum is found in the cytosol. Of this about 30% is bound in the metallothionein fraction. Isolated rat liver metallothionein reacts slowly with hydrolyzed cis-dichlorodiammine Pt(II). Thus, metallothionein is a major cellular site of binding of the platinum complex at concentrations which inhibit tumor growth.
D000818:Animals; D002104:Cadmium / Q000494:pharmacology; D002286:Carcinoma, Ehrlich Tumor / Q000378:metabolism*; D002451:Cell Compartmentation; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D002945:Cisplatin / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D008668:Metallothionein / Q000378:metabolism*; D009942:Organometallic Compounds; D051381:Rats; D013347:Subcellular Fractions / Q000378:metabolism; D013882:Thiosemicarbazones / Q000494:pharmacology; D015032:Zinc / Q000378:metabolism
D009942:Organometallic Compounds; D013882:Thiosemicarbazones; D002104:Cadmium; C015863:3-ethoxy-2-oxobutyraldehyde bis(thiosemicarbazonato)copper(II); D008668:Metallothionein; D015032:Zinc; D002945:Cisplatin