Bcl-2 overexpression decreases BCNU sensitivity of a human glioblastoma line through enhancement of catalase activity

Donatella Del Bufalo, Daniela Trisciuoglio, Annamaria Biroccio, Lucia Marcocci, Simonetta Buglioni, Antonio Candiloro, Marco Scarsella, Carlo Leonetti, Gabriella Zupi

Research output: Contribution to journalArticle

Abstract

The aim of this study was to evaluate the role of bcl-2 in 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) sensitivity of the ADFS human glioblastoma cell line in vitro and in vivo. To this end, the ADFS line expressing a low level of the bcl-2 protein was transfected with a bcl-2 expression vector. We found that bcl-2 overexpressing clones were less sensitive to in vitro BCNU treatment than the control clone. Cell cycle analysis demonstrated that while BCNU induced a consistent block in S/G2-M phases of the cell cycle in the control clone, it did not affect the cell cycle phase distribution of the two bcl-2 transfectants. The different sensitivity to BCNU was unrelated to the ability of bcl-2 to inhibit apoptosis, while bcl-2 appeared to protect bcl-2 transfectants from BCNU toxicity through an increase of catalase activity. The ability of the catalase inhibitor, sodium azide, to increase the BCNU sensitivity of the bcl-2 transfectants to levels of the BCNU-treated control clone substantiated the role of the catalase activity. The effect of bcl-2 in reducing sensitivity to BCNU was also confirmed by in vivo experiments. Xenografts of bcl-2 overexpressing tumors were less sensitive to BCNU treatment than xenografts originating from control cells.

Original languageEnglish
Pages (from-to)473-483
Number of pages11
JournalJournal of Cellular Biochemistry
Volume83
Issue number3
DOIs
Publication statusPublished - 2001

Fingerprint

Carmustine
Glioblastoma
Catalase
Clone Cells
Cells
Heterografts
Cell Cycle
Sodium Azide
G2 Phase
Cell Cycle Checkpoints
Cell Division
Toxicity
Tumors
Apoptosis
Cell Line

Keywords

  • Bcl-2
  • BCNU
  • Catalase
  • Glioblastoma

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology

Cite this

Bcl-2 overexpression decreases BCNU sensitivity of a human glioblastoma line through enhancement of catalase activity. / Bufalo, Donatella Del; Trisciuoglio, Daniela; Biroccio, Annamaria; Marcocci, Lucia; Buglioni, Simonetta; Candiloro, Antonio; Scarsella, Marco; Leonetti, Carlo; Zupi, Gabriella.

In: Journal of Cellular Biochemistry, Vol. 83, No. 3, 2001, p. 473-483.

Research output: Contribution to journalArticle

Bufalo, Donatella Del ; Trisciuoglio, Daniela ; Biroccio, Annamaria ; Marcocci, Lucia ; Buglioni, Simonetta ; Candiloro, Antonio ; Scarsella, Marco ; Leonetti, Carlo ; Zupi, Gabriella. / Bcl-2 overexpression decreases BCNU sensitivity of a human glioblastoma line through enhancement of catalase activity. In: Journal of Cellular Biochemistry. 2001 ; Vol. 83, No. 3. pp. 473-483.
@article{430c5a5480be4039af5ecbcb040ed866,
title = "Bcl-2 overexpression decreases BCNU sensitivity of a human glioblastoma line through enhancement of catalase activity",
abstract = "The aim of this study was to evaluate the role of bcl-2 in 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) sensitivity of the ADFS human glioblastoma cell line in vitro and in vivo. To this end, the ADFS line expressing a low level of the bcl-2 protein was transfected with a bcl-2 expression vector. We found that bcl-2 overexpressing clones were less sensitive to in vitro BCNU treatment than the control clone. Cell cycle analysis demonstrated that while BCNU induced a consistent block in S/G2-M phases of the cell cycle in the control clone, it did not affect the cell cycle phase distribution of the two bcl-2 transfectants. The different sensitivity to BCNU was unrelated to the ability of bcl-2 to inhibit apoptosis, while bcl-2 appeared to protect bcl-2 transfectants from BCNU toxicity through an increase of catalase activity. The ability of the catalase inhibitor, sodium azide, to increase the BCNU sensitivity of the bcl-2 transfectants to levels of the BCNU-treated control clone substantiated the role of the catalase activity. The effect of bcl-2 in reducing sensitivity to BCNU was also confirmed by in vivo experiments. Xenografts of bcl-2 overexpressing tumors were less sensitive to BCNU treatment than xenografts originating from control cells.",
keywords = "Bcl-2, BCNU, Catalase, Glioblastoma",
author = "Bufalo, {Donatella Del} and Daniela Trisciuoglio and Annamaria Biroccio and Lucia Marcocci and Simonetta Buglioni and Antonio Candiloro and Marco Scarsella and Carlo Leonetti and Gabriella Zupi",
year = "2001",
doi = "10.1002/jcb.1245",
language = "English",
volume = "83",
pages = "473--483",
journal = "Journal of Cellular Biochemistry",
issn = "0730-2312",
publisher = "Wiley-Liss Inc.",
number = "3",

}

TY - JOUR

T1 - Bcl-2 overexpression decreases BCNU sensitivity of a human glioblastoma line through enhancement of catalase activity

AU - Bufalo, Donatella Del

AU - Trisciuoglio, Daniela

AU - Biroccio, Annamaria

AU - Marcocci, Lucia

AU - Buglioni, Simonetta

AU - Candiloro, Antonio

AU - Scarsella, Marco

AU - Leonetti, Carlo

AU - Zupi, Gabriella

PY - 2001

Y1 - 2001

N2 - The aim of this study was to evaluate the role of bcl-2 in 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) sensitivity of the ADFS human glioblastoma cell line in vitro and in vivo. To this end, the ADFS line expressing a low level of the bcl-2 protein was transfected with a bcl-2 expression vector. We found that bcl-2 overexpressing clones were less sensitive to in vitro BCNU treatment than the control clone. Cell cycle analysis demonstrated that while BCNU induced a consistent block in S/G2-M phases of the cell cycle in the control clone, it did not affect the cell cycle phase distribution of the two bcl-2 transfectants. The different sensitivity to BCNU was unrelated to the ability of bcl-2 to inhibit apoptosis, while bcl-2 appeared to protect bcl-2 transfectants from BCNU toxicity through an increase of catalase activity. The ability of the catalase inhibitor, sodium azide, to increase the BCNU sensitivity of the bcl-2 transfectants to levels of the BCNU-treated control clone substantiated the role of the catalase activity. The effect of bcl-2 in reducing sensitivity to BCNU was also confirmed by in vivo experiments. Xenografts of bcl-2 overexpressing tumors were less sensitive to BCNU treatment than xenografts originating from control cells.

AB - The aim of this study was to evaluate the role of bcl-2 in 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) sensitivity of the ADFS human glioblastoma cell line in vitro and in vivo. To this end, the ADFS line expressing a low level of the bcl-2 protein was transfected with a bcl-2 expression vector. We found that bcl-2 overexpressing clones were less sensitive to in vitro BCNU treatment than the control clone. Cell cycle analysis demonstrated that while BCNU induced a consistent block in S/G2-M phases of the cell cycle in the control clone, it did not affect the cell cycle phase distribution of the two bcl-2 transfectants. The different sensitivity to BCNU was unrelated to the ability of bcl-2 to inhibit apoptosis, while bcl-2 appeared to protect bcl-2 transfectants from BCNU toxicity through an increase of catalase activity. The ability of the catalase inhibitor, sodium azide, to increase the BCNU sensitivity of the bcl-2 transfectants to levels of the BCNU-treated control clone substantiated the role of the catalase activity. The effect of bcl-2 in reducing sensitivity to BCNU was also confirmed by in vivo experiments. Xenografts of bcl-2 overexpressing tumors were less sensitive to BCNU treatment than xenografts originating from control cells.

KW - Bcl-2

KW - BCNU

KW - Catalase

KW - Glioblastoma

UR - http://www.scopus.com/inward/record.url?scp=0034763311&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0034763311&partnerID=8YFLogxK

U2 - 10.1002/jcb.1245

DO - 10.1002/jcb.1245

M3 - Article

C2 - 11596115

AN - SCOPUS:0034763311

VL - 83

SP - 473

EP - 483

JO - Journal of Cellular Biochemistry

JF - Journal of Cellular Biochemistry

SN - 0730-2312

IS - 3

ER -