Ormaplatin (also known as
tetraplatin) is a
platinum-containing analogue which has recently undergone clinical trials.
Ormaplatin may undergo conversion to dichloro(D,L-trans)-1,2-diaminocyclohexaneplatinum(II) [P1Cl2(trans-
dach)]. The
cisplatin-resistant murine
lymphoma cell lines E8 and E5, were found to be cross-resistant to
ormaplatin and
PtCl2(trans-dach). We found an inverse rank correlation between drug resistance and
drug accumulation for
PtCl2(trans-dach) similar to our previous findings with
cisplatin; however, accumulation of
ormaplatin in the resistant cells was increased.
Ormaplatin cytotoxicity appears to result primarily from extracellular conversion to
PtCl2(trans-dach), since
ormaplatin cytotoxicity was decreased under conditions where extracellular conversion to
PtCl2(trans-dach) was minimised. Co-incubation with different inhibitors of energy metabolism resulted in a 65-70% increase in
PtCl2(trans-dach) accumulation in the parental cell line R1.1 and
a 113-307% increase in the resistant cell line E5 which suggests that the decrease in accumulation in E5 may be at least partly energy dependent. We conclude from these findings that cross-resistance to
ormaplatin is associated with an energy-dependent decreased accumulation of
PtCl2(trans-dach) in these
cisplatin-resistant cell lines.