Pinpointing differences in cisplatin-induced apoptosis in adherent and non-adherent cancer cells

TY - JOUR

T1 - Pinpointing differences in cisplatin-induced apoptosis in adherent and non-adherent cancer cells

AU - Tastesen, Hanne Sørup

AU - Holm, Jacob Bak

AU - Poulsen, Kristian Arild

AU - Møller, Charlotte

AU - Stürup, Stefan

AU - Hoffmann, Else Kay

AU - Lambert, Ian Henry

N1 - Copyright © 2010 S. Karger AG, Basel.

PY - 2010/1/1

Y1 - 2010/1/1

N2 - 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.

AB - 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.

KW - Animals

KW - Antineoplastic Agents

KW - Apoptosis

KW - Caspase 3

KW - Cell Size

KW - Cisplatin

KW - Drug Resistance, Neoplasm

KW - Gene Knockdown Techniques

KW - Glutathione

KW - Membrane Glycoproteins

KW - Membrane Transport Proteins

KW - MicroRNAs

KW - Potassium

KW - Taurine

KW - Tumor Cells, Cultured

U2 - 10.1159/000323990

DO - 10.1159/000323990

M3 - Journal article

C2 - 21220912

SN - 1015-8987

VL - 26

SP - 809

EP - 820

JO - Cellular Physiology and Biochemistry

JF - Cellular Physiology and Biochemistry

IS - 6

ER -