bcl-2 protein inhibits etoposide-induced apoptosis through its effects on events subsequent to topoisomerase II-induced DNA strand breaks and their repair

Saori Kamesaki, Hiroshi Kamesaki, Timothy J. Jorgensen, Akihiko Tanizawa, Yves Pommier, Jeffrey Cossman

Research output: Contribution to journalArticle

Abstract

Previous studies have shown that bcl-2 overexpression can inhibit apoptosis induced by DNA-damaging agents widely used in cancer chemotherapy, including X-irradiation, alkylating agents (hydroperoxycyclo-phosphamide, etc.), and topoisomerase II inhibitors (etoposide, etc.). However, little is known about the mechanism by which bcl-2 overexpression inhibits apoptosis triggered by these agents. In this study, we examined whether bcl-2 overexpression could have effects on etoposide-induced DNA damage and its repair. For these experiments, we developed CH31 clones (mouse B-cells) stably transfected with human bcl-2 sense plasmids and compared these clones with a parental CH31 clone or CH31 clones with antisense plasmids. Overexpression of bcl-2 protein inhibited etoposide-induced apoptosis and cytotoxicity. However, there was no or little difference in the production and repair of DNA-protein cross-links, DNA single-strand breaks, and double-strand breaks among a parental CH31 clone and CH31 clones with human bcl-2 sense or antisense plasmids. These findings indicate that (a) apoptosis or cytotoxicity induced by etoposide can be separated into early events (formation of double-strand breaks. DNA single-strand breaks, and double-strand breaks) and later events (secondary DNA fragmentation or cell death) and (b) bcl-2 inhibits apoptosis and cytotoxicity induced by etoposide at some steps between these events.

Original languageEnglish (US)
Pages (from-to)4251-4256
Number of pages6
JournalCancer Research
Volume53
Issue number18
StatePublished - Sep 15 1993
Externally publishedYes

Fingerprint

Type II DNA Topoisomerase
DNA Breaks
Etoposide
Clone Cells
Apoptosis
Single-Stranded DNA Breaks
Proteins
Plasmids
Dimethoate
Topoisomerase II Inhibitors
Alkylating Agents
DNA Fragmentation
DNA Repair
DNA Damage
B-Lymphocytes
Cell Death
Drug Therapy
DNA
Neoplasms

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Kamesaki, S., Kamesaki, H., Jorgensen, T. J., Tanizawa, A., Pommier, Y., & Cossman, J. (1993). bcl-2 protein inhibits etoposide-induced apoptosis through its effects on events subsequent to topoisomerase II-induced DNA strand breaks and their repair. Cancer Research, 53(18), 4251-4256.

bcl-2 protein inhibits etoposide-induced apoptosis through its effects on events subsequent to topoisomerase II-induced DNA strand breaks and their repair. / Kamesaki, Saori; Kamesaki, Hiroshi; Jorgensen, Timothy J.; Tanizawa, Akihiko; Pommier, Yves; Cossman, Jeffrey.

In: Cancer Research, Vol. 53, No. 18, 15.09.1993, p. 4251-4256.

Research output: Contribution to journalArticle

Kamesaki, S, Kamesaki, H, Jorgensen, TJ, Tanizawa, A, Pommier, Y & Cossman, J 1993, 'bcl-2 protein inhibits etoposide-induced apoptosis through its effects on events subsequent to topoisomerase II-induced DNA strand breaks and their repair', Cancer Research, vol. 53, no. 18, pp. 4251-4256.
Kamesaki, Saori ; Kamesaki, Hiroshi ; Jorgensen, Timothy J. ; Tanizawa, Akihiko ; Pommier, Yves ; Cossman, Jeffrey. / bcl-2 protein inhibits etoposide-induced apoptosis through its effects on events subsequent to topoisomerase II-induced DNA strand breaks and their repair. In: Cancer Research. 1993 ; Vol. 53, No. 18. pp. 4251-4256.
@article{1ac143dab72546f287446409a11565e2,
title = "bcl-2 protein inhibits etoposide-induced apoptosis through its effects on events subsequent to topoisomerase II-induced DNA strand breaks and their repair",
abstract = "Previous studies have shown that bcl-2 overexpression can inhibit apoptosis induced by DNA-damaging agents widely used in cancer chemotherapy, including X-irradiation, alkylating agents (hydroperoxycyclo-phosphamide, etc.), and topoisomerase II inhibitors (etoposide, etc.). However, little is known about the mechanism by which bcl-2 overexpression inhibits apoptosis triggered by these agents. In this study, we examined whether bcl-2 overexpression could have effects on etoposide-induced DNA damage and its repair. For these experiments, we developed CH31 clones (mouse B-cells) stably transfected with human bcl-2 sense plasmids and compared these clones with a parental CH31 clone or CH31 clones with antisense plasmids. Overexpression of bcl-2 protein inhibited etoposide-induced apoptosis and cytotoxicity. However, there was no or little difference in the production and repair of DNA-protein cross-links, DNA single-strand breaks, and double-strand breaks among a parental CH31 clone and CH31 clones with human bcl-2 sense or antisense plasmids. These findings indicate that (a) apoptosis or cytotoxicity induced by etoposide can be separated into early events (formation of double-strand breaks. DNA single-strand breaks, and double-strand breaks) and later events (secondary DNA fragmentation or cell death) and (b) bcl-2 inhibits apoptosis and cytotoxicity induced by etoposide at some steps between these events.",
author = "Saori Kamesaki and Hiroshi Kamesaki and Jorgensen, {Timothy J.} and Akihiko Tanizawa and Yves Pommier and Jeffrey Cossman",
year = "1993",
month = "9",
day = "15",
language = "English (US)",
volume = "53",
pages = "4251--4256",
journal = "Journal of Cancer Research",
issn = "0099-7013",
publisher = "American Association for Cancer Research Inc.",
number = "18",

}

TY - JOUR

T1 - bcl-2 protein inhibits etoposide-induced apoptosis through its effects on events subsequent to topoisomerase II-induced DNA strand breaks and their repair

AU - Kamesaki, Saori

AU - Kamesaki, Hiroshi

AU - Jorgensen, Timothy J.

AU - Tanizawa, Akihiko

AU - Pommier, Yves

AU - Cossman, Jeffrey

PY - 1993/9/15

Y1 - 1993/9/15

N2 - Previous studies have shown that bcl-2 overexpression can inhibit apoptosis induced by DNA-damaging agents widely used in cancer chemotherapy, including X-irradiation, alkylating agents (hydroperoxycyclo-phosphamide, etc.), and topoisomerase II inhibitors (etoposide, etc.). However, little is known about the mechanism by which bcl-2 overexpression inhibits apoptosis triggered by these agents. In this study, we examined whether bcl-2 overexpression could have effects on etoposide-induced DNA damage and its repair. For these experiments, we developed CH31 clones (mouse B-cells) stably transfected with human bcl-2 sense plasmids and compared these clones with a parental CH31 clone or CH31 clones with antisense plasmids. Overexpression of bcl-2 protein inhibited etoposide-induced apoptosis and cytotoxicity. However, there was no or little difference in the production and repair of DNA-protein cross-links, DNA single-strand breaks, and double-strand breaks among a parental CH31 clone and CH31 clones with human bcl-2 sense or antisense plasmids. These findings indicate that (a) apoptosis or cytotoxicity induced by etoposide can be separated into early events (formation of double-strand breaks. DNA single-strand breaks, and double-strand breaks) and later events (secondary DNA fragmentation or cell death) and (b) bcl-2 inhibits apoptosis and cytotoxicity induced by etoposide at some steps between these events.

AB - Previous studies have shown that bcl-2 overexpression can inhibit apoptosis induced by DNA-damaging agents widely used in cancer chemotherapy, including X-irradiation, alkylating agents (hydroperoxycyclo-phosphamide, etc.), and topoisomerase II inhibitors (etoposide, etc.). However, little is known about the mechanism by which bcl-2 overexpression inhibits apoptosis triggered by these agents. In this study, we examined whether bcl-2 overexpression could have effects on etoposide-induced DNA damage and its repair. For these experiments, we developed CH31 clones (mouse B-cells) stably transfected with human bcl-2 sense plasmids and compared these clones with a parental CH31 clone or CH31 clones with antisense plasmids. Overexpression of bcl-2 protein inhibited etoposide-induced apoptosis and cytotoxicity. However, there was no or little difference in the production and repair of DNA-protein cross-links, DNA single-strand breaks, and double-strand breaks among a parental CH31 clone and CH31 clones with human bcl-2 sense or antisense plasmids. These findings indicate that (a) apoptosis or cytotoxicity induced by etoposide can be separated into early events (formation of double-strand breaks. DNA single-strand breaks, and double-strand breaks) and later events (secondary DNA fragmentation or cell death) and (b) bcl-2 inhibits apoptosis and cytotoxicity induced by etoposide at some steps between these events.

UR - http://www.scopus.com/inward/record.url?scp=0027892521&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0027892521&partnerID=8YFLogxK

M3 - Article

VL - 53

SP - 4251

EP - 4256

JO - Journal of Cancer Research

JF - Journal of Cancer Research

SN - 0099-7013

IS - 18

ER -