Arsenic trioxide induces apoptosis through a reactive oxygen species-dependent pathway and loss of mitochondrial membrane potential in HeLa cells.

Sang Hyeok Woo, In Chul Park, Myung Jin Park, Hyung Chahn Lee, Su Jae Lee, Yong Jin Chun, Seung Hoon Lee, Seok Il Hong, Chang Hun Rhee

Research output: Contribution to journalArticle

137 Citations (Scopus)

Abstract

Arsenic trioxide (As2O3) can induce clinical remission in patients with acute promyelocytic leukemia (APL) through induction of apoptosis. To investigate the potential therapeutic usage of As2O3 in cervical cancer and its possible mechanisms, human cervical cancer cell line HeLa was employed. The cells underwent apoptosis in response to As2O3, accompanied by a decrease of mitochondrial membrane potential and caspase-3 activation. Overexpression of Bcl-2, however, prevented the dissipation of mitochondrial membrane potential, subsequently protecting the cells from As2O3-induced apoptosis. As2O3 increased cellular content of reactive oxygen species (ROS), especially hydrogen peroxide (H2O2), and the antioxidant N-acetyl-L-cysteine completely suppressed As2O3-induced apoptosis. Furthermore, incubation of the cells with catalase resulted in significant suppression of As2O3-induced apoptosis. The above results indicate that the induction of HeLa cell apoptosis by As2O3 involved an early decrease in cellular mitochondrial membrane potential and increase in ROS content, predominantly H2O2, followed by caspase-3 activation and DNA fragmentation.

Original languageEnglish
Pages (from-to)57-63
Number of pages7
JournalInternational Journal of Oncology
Volume21
Issue number1
StatePublished - 2002 Jul

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Mitochondrial Membrane Potential
HeLa Cells
Reactive Oxygen Species
Apoptosis
Caspase 3
Uterine Cervical Neoplasms
arsenic trioxide
Acute Promyelocytic Leukemia
Acetylcysteine
DNA Fragmentation
Catalase
Hydrogen Peroxide
Antioxidants
Cell Line

Cite this

Woo, Sang Hyeok ; Park, In Chul ; Park, Myung Jin ; Lee, Hyung Chahn ; Lee, Su Jae ; Chun, Yong Jin ; Lee, Seung Hoon ; Hong, Seok Il ; Rhee, Chang Hun. / Arsenic trioxide induces apoptosis through a reactive oxygen species-dependent pathway and loss of mitochondrial membrane potential in HeLa cells. In: International Journal of Oncology. 2002 ; Vol. 21, No. 1. pp. 57-63.
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abstract = "Arsenic trioxide (As2O3) can induce clinical remission in patients with acute promyelocytic leukemia (APL) through induction of apoptosis. To investigate the potential therapeutic usage of As2O3 in cervical cancer and its possible mechanisms, human cervical cancer cell line HeLa was employed. The cells underwent apoptosis in response to As2O3, accompanied by a decrease of mitochondrial membrane potential and caspase-3 activation. Overexpression of Bcl-2, however, prevented the dissipation of mitochondrial membrane potential, subsequently protecting the cells from As2O3-induced apoptosis. As2O3 increased cellular content of reactive oxygen species (ROS), especially hydrogen peroxide (H2O2), and the antioxidant N-acetyl-L-cysteine completely suppressed As2O3-induced apoptosis. Furthermore, incubation of the cells with catalase resulted in significant suppression of As2O3-induced apoptosis. The above results indicate that the induction of HeLa cell apoptosis by As2O3 involved an early decrease in cellular mitochondrial membrane potential and increase in ROS content, predominantly H2O2, followed by caspase-3 activation and DNA fragmentation.",
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Arsenic trioxide induces apoptosis through a reactive oxygen species-dependent pathway and loss of mitochondrial membrane potential in HeLa cells. / Woo, Sang Hyeok; Park, In Chul; Park, Myung Jin; Lee, Hyung Chahn; Lee, Su Jae; Chun, Yong Jin; Lee, Seung Hoon; Hong, Seok Il; Rhee, Chang Hun.

In: International Journal of Oncology, Vol. 21, No. 1, 07.2002, p. 57-63.

Research output: Contribution to journalArticle

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AU - Park, In Chul

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AU - Lee, Su Jae

AU - Chun, Yong Jin

AU - Lee, Seung Hoon

AU - Hong, Seok Il

AU - Rhee, Chang Hun

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AB - Arsenic trioxide (As2O3) can induce clinical remission in patients with acute promyelocytic leukemia (APL) through induction of apoptosis. To investigate the potential therapeutic usage of As2O3 in cervical cancer and its possible mechanisms, human cervical cancer cell line HeLa was employed. The cells underwent apoptosis in response to As2O3, accompanied by a decrease of mitochondrial membrane potential and caspase-3 activation. Overexpression of Bcl-2, however, prevented the dissipation of mitochondrial membrane potential, subsequently protecting the cells from As2O3-induced apoptosis. As2O3 increased cellular content of reactive oxygen species (ROS), especially hydrogen peroxide (H2O2), and the antioxidant N-acetyl-L-cysteine completely suppressed As2O3-induced apoptosis. Furthermore, incubation of the cells with catalase resulted in significant suppression of As2O3-induced apoptosis. The above results indicate that the induction of HeLa cell apoptosis by As2O3 involved an early decrease in cellular mitochondrial membrane potential and increase in ROS content, predominantly H2O2, followed by caspase-3 activation and DNA fragmentation.

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