Pinpointing differences in cisplatin-induced apoptosis in adherent and non-adherent cancer cells
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Pinpointing differences in cisplatin-induced apoptosis in adherent and non-adherent cancer cells. / Tastesen, Hanne Sørup; Holm, Jacob Bak; Poulsen, Kristian Arild; Møller, Charlotte; Stürup, Stefan; Hoffmann, Else Kay; Lambert, Ian Henry.
I: Cellular Physiology and Biochemistry, Bind 26, Nr. 6, 01.01.2010, s. 809-820.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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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
VL - 26
SP - 809
EP - 820
JO - Cellular Physiology and Biochemistry
JF - Cellular Physiology and Biochemistry
SN - 1015-8987
IS - 6
ER -
ID: 32441969