Arsenic trioxide and radiation enhance apoptotic effects in HL-60 cells through increased ROS generation and regulation of JNK and p38 MAPK signaling pathways

Sheng Yow Ho, Wei Wu, Hui Wen Chiu, Yi An Chen, Yuan Soon Ho, How Ran Guo, Ying Jan Wang

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

The induction of apoptotic cell death is a significant mechanism of tumor cells under the influence of radio-/chemotherapy, and resistance to these treatments has been linked to some cancer cell lines with a low propensity for apoptosis. The present study aimed to investigate the enhanced effects and mechanisms in apoptosis and the cycle distribution of HL-60 cells, a human leukemia cell line lacking a functional p53 protein, after combination treatment with arsenic trioxide (ATO) and irradiation (IR). Our results indicated that combined treatment led to increased cytotoxicity and apoptotic cell death in HL-60 cells, which was correlated with the activation of cdc-2 and increased expression of cyclin B, the induction of intracellular reactive oxygen species (ROS) generation, the loss of mitochondria membrane potential, and the activation of caspase-3. The combined treatment of HL-60 cells pre-treated with Z-VAD or NAC resulted in a significant reduction in apoptotic cells. In addition, activation of JNK and p38 MAPK may be involved in combined treatment-mediated apoptosis. The data suggest that a combination of IR and ATO could be a potential therapeutic strategy against p53-deficient leukemia cells.

Original languageEnglish
Pages (from-to)162-171
Number of pages10
JournalChemico-Biological Interactions
Volume193
Issue number2
DOIs
Publication statusPublished - Sep 5 2011
Externally publishedYes

Fingerprint

HL-60 Cells
p38 Mitogen-Activated Protein Kinases
Reactive Oxygen Species
Cells
Radiation
Chemical activation
Cell death
Apoptosis
Irradiation
Cyclin B
Mitochondria
Chemotherapy
Leukemia
Cell Death
Therapeutics
Cytotoxicity
Caspase 3
Tumors
Cell Line
Membranes

Keywords

  • Apoptosis
  • Arsenic trioxide
  • HL-60
  • Irradiation

ASJC Scopus subject areas

  • Toxicology

Cite this

Arsenic trioxide and radiation enhance apoptotic effects in HL-60 cells through increased ROS generation and regulation of JNK and p38 MAPK signaling pathways. / Ho, Sheng Yow; Wu, Wei; Chiu, Hui Wen; Chen, Yi An; Ho, Yuan Soon; Guo, How Ran; Wang, Ying Jan.

In: Chemico-Biological Interactions, Vol. 193, No. 2, 05.09.2011, p. 162-171.

Research output: Contribution to journalArticle

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