Platinum compounds are used in the treatment of
cancer. We demonstrate that
cisplatin-induced (10 μM) apoptosis (caspase-3 activity) is pronounced within 18 hours in non-adherent Ehrlich
ascites tumour cells (EATC), whereas there is no increase in
caspase-3 activity in the adherent Ehrlich Lettré
ascites tumour cells (ELA). Loss of KCl and cell shrinkage are hallmarks in apoptosis and has been shown in EATC. However, we find no reduction in cell volume and only a minor loss of K(+) which is accompanied by net uptake of Na(+) following 18 hours
cisplatin exposure in ELA.
Glutathione and
taurine have previously been demonstrated to protect cells from apoptosis. We find, however, that increase or decrease in the cellular content of
glutathione and
taurine has no effect on
cisplatin-induced cell death in EATC and ELA. Nevertheless, knock-down of the
taurine transporter TauT leads to a significant increase in apoptosis in ELA following
cisplatin exposure. We find that cytosolic accumulation of
cisplatin is similar in EATC and ELA. However, the nuclear accumulation and
DNA-binding of
cisplatin is significant lower in ELA compared to EATC. We suggest three putative reasons for the observed
cisplatin insensitivity in the adherent
tumor cells (ELA) compared to the non-adherent
tumor cells (EATC): less nuclear
cisplatin accumulation, increased TauT activity, and decreased
anion and water loss.