Glutathione transferase omega 1-1 (GSTO1-1) plays an anti-apoptotic role in cell resistance to cisplatin toxicity

Simona Piaggi, Chiara Raggi, Alessandro Corti, Emanuela Pitzalis, Marco C. Mascherpa, Michela Saviozzi, Alfonso Pompella, Alessandro F. Casini

Research output: Contribution to journalArticle

53 Citations (Scopus)

Abstract

Several lines of evidence correlate the overexpression of glutathione S-transferase omega 1-1 (GSTO1-1) with the onset of drug resistance of cancer cells; however, no direct evidence is yet available. In order to investigate the mechanisms involved, stable transfection with GSTO1-1 complementary DNA was performed in HeLa cells, which spontaneously express very low levels of GSTO1-1. When transfected cells were seeded at low density, a sharp increase in GSTO1-1 expression was observed as compared with controls, along with an increased resistance against cisplatin cytotoxicity. When seeded at increasing densities, control untransfected cells also presented with an increase in GSTO1-1 expression, again accompanied by cisplatin resistance; the latter was significantly reduced after transfection with GSTO1-1 small interfering RNA. Cisplatin resistance of transfected cells was not accounted for by changes in the intracellular drug concentration nor in the amount of DNA cross-links or content of glutathione. Rather, transfected cells presented with a marked decrease of apoptosis as compared with controls, suggesting that GSTO1-1 overexpression may prevent cisplatin toxicity by interfering with the apoptotic process. Cisplatin treatment was in fact followed at early times (1-2 h) by activation of both Akt kinase and extracellular signal-regulated kinase (ERK)-1/2 in the transfected cells but not in controls. Conversely, in transfected cells, the strong activation of Jun N-terminal kinase (JNK)-1 induced by cisplatin at later times (10-20 h) was completely prevented. In conclusion, GSTO1-1 overexpression appears to be associated with activation of survival pathways (Akt and ERK1/2) and inhibition of apoptotic pathways (JNK1), as well as protection against cisplatin-induced apoptosis.

Original languageEnglish
Pages (from-to)804-811
Number of pages8
JournalCarcinogenesis
Volume31
Issue number5
DOIs
Publication statusPublished - Jan 27 2010

Fingerprint

Glutathione Transferase
Cisplatin
Transfection
Phosphotransferases
Apoptosis
Mitogen-Activated Protein Kinase 3
MAP Kinase Signaling System
Mitogen-Activated Protein Kinase 1
HeLa Cells
Drug Resistance
Small Interfering RNA
Glutathione
Complementary DNA
DNA
Pharmaceutical Preparations
Neoplasms

ASJC Scopus subject areas

  • Cancer Research

Cite this

Glutathione transferase omega 1-1 (GSTO1-1) plays an anti-apoptotic role in cell resistance to cisplatin toxicity. / Piaggi, Simona; Raggi, Chiara; Corti, Alessandro; Pitzalis, Emanuela; Mascherpa, Marco C.; Saviozzi, Michela; Pompella, Alfonso; Casini, Alessandro F.

In: Carcinogenesis, Vol. 31, No. 5, 27.01.2010, p. 804-811.

Research output: Contribution to journalArticle

Piaggi, S, Raggi, C, Corti, A, Pitzalis, E, Mascherpa, MC, Saviozzi, M, Pompella, A & Casini, AF 2010, 'Glutathione transferase omega 1-1 (GSTO1-1) plays an anti-apoptotic role in cell resistance to cisplatin toxicity', Carcinogenesis, vol. 31, no. 5, pp. 804-811. https://doi.org/10.1093/carcin/bgq031
Piaggi, Simona ; Raggi, Chiara ; Corti, Alessandro ; Pitzalis, Emanuela ; Mascherpa, Marco C. ; Saviozzi, Michela ; Pompella, Alfonso ; Casini, Alessandro F. / Glutathione transferase omega 1-1 (GSTO1-1) plays an anti-apoptotic role in cell resistance to cisplatin toxicity. In: Carcinogenesis. 2010 ; Vol. 31, No. 5. pp. 804-811.
@article{61d8a511fe194a3cb456327c41b4e51c,
title = "Glutathione transferase omega 1-1 (GSTO1-1) plays an anti-apoptotic role in cell resistance to cisplatin toxicity",
abstract = "Several lines of evidence correlate the overexpression of glutathione S-transferase omega 1-1 (GSTO1-1) with the onset of drug resistance of cancer cells; however, no direct evidence is yet available. In order to investigate the mechanisms involved, stable transfection with GSTO1-1 complementary DNA was performed in HeLa cells, which spontaneously express very low levels of GSTO1-1. When transfected cells were seeded at low density, a sharp increase in GSTO1-1 expression was observed as compared with controls, along with an increased resistance against cisplatin cytotoxicity. When seeded at increasing densities, control untransfected cells also presented with an increase in GSTO1-1 expression, again accompanied by cisplatin resistance; the latter was significantly reduced after transfection with GSTO1-1 small interfering RNA. Cisplatin resistance of transfected cells was not accounted for by changes in the intracellular drug concentration nor in the amount of DNA cross-links or content of glutathione. Rather, transfected cells presented with a marked decrease of apoptosis as compared with controls, suggesting that GSTO1-1 overexpression may prevent cisplatin toxicity by interfering with the apoptotic process. Cisplatin treatment was in fact followed at early times (1-2 h) by activation of both Akt kinase and extracellular signal-regulated kinase (ERK)-1/2 in the transfected cells but not in controls. Conversely, in transfected cells, the strong activation of Jun N-terminal kinase (JNK)-1 induced by cisplatin at later times (10-20 h) was completely prevented. In conclusion, GSTO1-1 overexpression appears to be associated with activation of survival pathways (Akt and ERK1/2) and inhibition of apoptotic pathways (JNK1), as well as protection against cisplatin-induced apoptosis.",
author = "Simona Piaggi and Chiara Raggi and Alessandro Corti and Emanuela Pitzalis and Mascherpa, {Marco C.} and Michela Saviozzi and Alfonso Pompella and Casini, {Alessandro F.}",
year = "2010",
month = "1",
day = "27",
doi = "10.1093/carcin/bgq031",
language = "English",
volume = "31",
pages = "804--811",
journal = "Carcinogenesis",
issn = "0143-3334",
publisher = "Oxford University Press",
number = "5",

}

TY - JOUR

T1 - Glutathione transferase omega 1-1 (GSTO1-1) plays an anti-apoptotic role in cell resistance to cisplatin toxicity

AU - Piaggi, Simona

AU - Raggi, Chiara

AU - Corti, Alessandro

AU - Pitzalis, Emanuela

AU - Mascherpa, Marco C.

AU - Saviozzi, Michela

AU - Pompella, Alfonso

AU - Casini, Alessandro F.

PY - 2010/1/27

Y1 - 2010/1/27

N2 - Several lines of evidence correlate the overexpression of glutathione S-transferase omega 1-1 (GSTO1-1) with the onset of drug resistance of cancer cells; however, no direct evidence is yet available. In order to investigate the mechanisms involved, stable transfection with GSTO1-1 complementary DNA was performed in HeLa cells, which spontaneously express very low levels of GSTO1-1. When transfected cells were seeded at low density, a sharp increase in GSTO1-1 expression was observed as compared with controls, along with an increased resistance against cisplatin cytotoxicity. When seeded at increasing densities, control untransfected cells also presented with an increase in GSTO1-1 expression, again accompanied by cisplatin resistance; the latter was significantly reduced after transfection with GSTO1-1 small interfering RNA. Cisplatin resistance of transfected cells was not accounted for by changes in the intracellular drug concentration nor in the amount of DNA cross-links or content of glutathione. Rather, transfected cells presented with a marked decrease of apoptosis as compared with controls, suggesting that GSTO1-1 overexpression may prevent cisplatin toxicity by interfering with the apoptotic process. Cisplatin treatment was in fact followed at early times (1-2 h) by activation of both Akt kinase and extracellular signal-regulated kinase (ERK)-1/2 in the transfected cells but not in controls. Conversely, in transfected cells, the strong activation of Jun N-terminal kinase (JNK)-1 induced by cisplatin at later times (10-20 h) was completely prevented. In conclusion, GSTO1-1 overexpression appears to be associated with activation of survival pathways (Akt and ERK1/2) and inhibition of apoptotic pathways (JNK1), as well as protection against cisplatin-induced apoptosis.

AB - Several lines of evidence correlate the overexpression of glutathione S-transferase omega 1-1 (GSTO1-1) with the onset of drug resistance of cancer cells; however, no direct evidence is yet available. In order to investigate the mechanisms involved, stable transfection with GSTO1-1 complementary DNA was performed in HeLa cells, which spontaneously express very low levels of GSTO1-1. When transfected cells were seeded at low density, a sharp increase in GSTO1-1 expression was observed as compared with controls, along with an increased resistance against cisplatin cytotoxicity. When seeded at increasing densities, control untransfected cells also presented with an increase in GSTO1-1 expression, again accompanied by cisplatin resistance; the latter was significantly reduced after transfection with GSTO1-1 small interfering RNA. Cisplatin resistance of transfected cells was not accounted for by changes in the intracellular drug concentration nor in the amount of DNA cross-links or content of glutathione. Rather, transfected cells presented with a marked decrease of apoptosis as compared with controls, suggesting that GSTO1-1 overexpression may prevent cisplatin toxicity by interfering with the apoptotic process. Cisplatin treatment was in fact followed at early times (1-2 h) by activation of both Akt kinase and extracellular signal-regulated kinase (ERK)-1/2 in the transfected cells but not in controls. Conversely, in transfected cells, the strong activation of Jun N-terminal kinase (JNK)-1 induced by cisplatin at later times (10-20 h) was completely prevented. In conclusion, GSTO1-1 overexpression appears to be associated with activation of survival pathways (Akt and ERK1/2) and inhibition of apoptotic pathways (JNK1), as well as protection against cisplatin-induced apoptosis.

UR - http://www.scopus.com/inward/record.url?scp=77952310056&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77952310056&partnerID=8YFLogxK

U2 - 10.1093/carcin/bgq031

DO - 10.1093/carcin/bgq031

M3 - Article

C2 - 20106899

AN - SCOPUS:77952310056

VL - 31

SP - 804

EP - 811

JO - Carcinogenesis

JF - Carcinogenesis

SN - 0143-3334

IS - 5

ER -