The fate of platinum(II) and platinum(IV) anti-cancer agents in cancer cells and tumours.
SRIXE mapping has been used to gain insight into the fate of platinum(II) and platinum(IV) complexes in cells and tumours treated with anticancer active complexes to facilitate the development of improved drugs. SRIXE maps were collected of thin sections of human ovarian (A2780) cancer cells treated with bromine containing platinum complexes, cis-[PtCl(2)(3-Brpyr)(NH(3))] (3-Brpyr=3-bromopyridine) and cis,trans,cis-[PtCl(2)(OAcBr)(2)(NH(3))(2)] (OAcBr=bromoacetate), or a platinum complex with an intercalator attached cis-[PtCl(2)(2-[(3-aminopropyl)amino]-9,10-anthracenedione)(NH(3))]. After 24h the complexes appear to be localised in the cell nucleus with a lower concentration in the surrounding cytoplasm. In cells treated with cis-[PtCl(2)(3-Brpyr)(NH(3))] the concentration of bromine was substantially higher than in control cells and the bromine was co-localised with the platinum consistent with the 3-bromopyridine ligand remaining bound to the platinum. The cells treated with cis,trans,cis-[PtCl(2)(OAcBr)(2)(NH(3))(2)] also showed an increased level of bromine, but to a much lesser extent than for those treated with cis-[PtCl(2)(3-Brpyr)(NH(3))] suggestive of substantial reduction of the platinum(IV) complex. Maps were also collected from thin sections of a 4T1.2 neo 1 mammary tumour xenograft removed from a mouse 3h after treatment with cis,trans,cis-[PtCl(2)(OH)(2)(NH(3))(2)] and revealed selective uptake of platinum by one cell.
Hall
Matthew D
MD
Centre for Heavy Metals Research, School of Chemistry F11, The University of Sydney, NSW 2006, Australia.
Alderden
Rebecca A
RA
Zhang
Mei
M
Beale
Philip J
PJ
Cai
Zhonghou
Z
Lai
Barry
B
Stampfl
Anton P J
AP
Hambley
Trevor W
TW
D000818:Animals; D000970:Antineoplastic Agents / Q000493:pharmacokinetics*; D017605:Bromine Compounds / Q000032:analysis; D004577:Electron Probe Microanalysis / Q000379:methods*; D005260:Female; D006801:Humans; D007364:Intercalating Agents / Q000493:pharmacokinetics; D015674:Mammary Neoplasms, Animal / Q000000981:diagnostic imaging / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D009369:Neoplasms / Q000000981:diagnostic imaging / Q000378:metabolism*; D009944:Organoplatinum Compounds / Q000493:pharmacokinetics*; D010051:Ovarian Neoplasms / Q000000981:diagnostic imaging / Q000378:metabolism; D011859:Radiography; D023041:Xenograft Model Antitumor Assays
D000970:Antineoplastic Agents; D017605:Bromine Compounds; D007364:Intercalating Agents; D009944:Organoplatinum Compounds