Head and neck cancer cell lines are resistant to mitochondrial- depolarization-induced apoptosis

Ming Zhao, Wojciech Mydlarz, Shaoyu Zhou, Joseph Califano

Research output: Contribution to journalArticle

Abstract

Purpose: Mitochondrial dysfunction has been linked to defects in the apoptotic pathway, and solid tumors, including head and neck squamous cell carcinoma (HNSCC), exhibit defects in apoptosis. Loss of mitochondrial membrane potential (ΔΨm) is an early initiating event in the mitochondrial apoptotic pathway. We investigated the apoptotic response of 3 head and neck cancer cell lines treated with a mitochondrial-membrane-depolarizing agent, valinomycin, and studied the ability of depolarization to induce release of cytochrome c in these cell lines. Experimental Design: HNSCC cell lines JHU-011, -012 and -019, and a leukemia control cell line HL-60 were assayed for ΔΨm after valinomycin treatment by staining with mitochondrial- membrane-potential-specific probe JC-1 and stained with apoptosis-specific probe annexin-V to measure their rate of apoptosis by FACS. Western blotting was also applied to detect cytoplasmic cytochrome c release. Results: ΔΨm in head and neck cell lines started to show slight loss of ΔΨm, while HL-60 showed significant loss of ΔΨm after 30 min of treatment. All cell lines demonstrated complete mitochondrial depolarization within 24 h, however, only the control cell line HL-60 underwent apoptosis. In addition, HNSCC cell lines did not demonstrate cytoplasmic cytochrome c release despite significant mitochondrial membrane depolarization, while HL-60 cell initiated apoptosis and cytochcrome c release after 24 h of treatment. Conclusions: Head and neck cancer cell lines exhibit defects in mitochondrial-membrane- depolarization-induced apoptosis as well as impaired release of cytochrome c despite significant mitochondrial membrane depolarization. Proximal defects in the mitochondrial apoptosis pathway are a feature of HNSCC.

Original languageEnglish (US)
Pages (from-to)257-263
Number of pages7
JournalORL
Volume70
Issue number4
DOIs
StatePublished - Jun 2008

Fingerprint

Head and Neck Neoplasms
Apoptosis
Cell Line
Mitochondrial Membranes
Cytochromes c
Valinomycin
Mitochondrial Membrane Potential
HL-60 Cells
Annexin A5
Leukemia
Research Design
Neck
Western Blotting
Head
Staining and Labeling
Carcinoma, squamous cell of head and neck

Keywords

  • Apoptosis
  • Head and neck cancer cell lines
  • Mitochondrial depolarization

ASJC Scopus subject areas

  • Otorhinolaryngology

Cite this

Head and neck cancer cell lines are resistant to mitochondrial- depolarization-induced apoptosis. / Zhao, Ming; Mydlarz, Wojciech; Zhou, Shaoyu; Califano, Joseph.

In: ORL, Vol. 70, No. 4, 06.2008, p. 257-263.

Research output: Contribution to journalArticle

Zhao, Ming ; Mydlarz, Wojciech ; Zhou, Shaoyu ; Califano, Joseph. / Head and neck cancer cell lines are resistant to mitochondrial- depolarization-induced apoptosis. In: ORL. 2008 ; Vol. 70, No. 4. pp. 257-263.
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AB - Purpose: Mitochondrial dysfunction has been linked to defects in the apoptotic pathway, and solid tumors, including head and neck squamous cell carcinoma (HNSCC), exhibit defects in apoptosis. Loss of mitochondrial membrane potential (ΔΨm) is an early initiating event in the mitochondrial apoptotic pathway. We investigated the apoptotic response of 3 head and neck cancer cell lines treated with a mitochondrial-membrane-depolarizing agent, valinomycin, and studied the ability of depolarization to induce release of cytochrome c in these cell lines. Experimental Design: HNSCC cell lines JHU-011, -012 and -019, and a leukemia control cell line HL-60 were assayed for ΔΨm after valinomycin treatment by staining with mitochondrial- membrane-potential-specific probe JC-1 and stained with apoptosis-specific probe annexin-V to measure their rate of apoptosis by FACS. Western blotting was also applied to detect cytoplasmic cytochrome c release. Results: ΔΨm in head and neck cell lines started to show slight loss of ΔΨm, while HL-60 showed significant loss of ΔΨm after 30 min of treatment. All cell lines demonstrated complete mitochondrial depolarization within 24 h, however, only the control cell line HL-60 underwent apoptosis. In addition, HNSCC cell lines did not demonstrate cytoplasmic cytochrome c release despite significant mitochondrial membrane depolarization, while HL-60 cell initiated apoptosis and cytochcrome c release after 24 h of treatment. Conclusions: Head and neck cancer cell lines exhibit defects in mitochondrial-membrane- depolarization-induced apoptosis as well as impaired release of cytochrome c despite significant mitochondrial membrane depolarization. Proximal defects in the mitochondrial apoptosis pathway are a feature of HNSCC.

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