Hydrogen peroxide inhibits non-small cell lung cancer cell anoikis through the inhibition of caveolin-1 degradation

Pimuma Rungtabnapa, Ubonthip Nimmannit, Hasseri Halim, Yon Rojanasakul, Pithi Chanvorachote

Research output: Contribution to journalArticle

51 Citations (Scopus)

Abstract

Anoikis or detachment-induced apoptosis plays an essential role in the regulation of cancer cell metastasis. Caveolin-1 (Cav-1) is a key protein involved in tumor metastasis, but its role in anoikis and its regulation during cell detachment are unclear. We report here that Cav-1 plays a key role as a negative regulator of anoikis through a reactive oxygen species (ROS)-dependent mechanism in human lung carcinoma H460 cells. During cell detachment, Cav-1 is downregulated, whereas ROS generation is upregulated. Hydrogen peroxide and hydroxyl radical are two key ROS produced by cells during detachment. Treatment of the cells with hydrogen peroxide scavengers, catalase and N-acetylcysteine, promoted Cav-1 downregulation and anoikis during cell detachment, indicating that produced hydrogen peroxide plays a primary role in preventing anoikis by stabilizing Cav-1 protein. Catalase and N-acetylcysteine promoted ubiquitination and proteasomal degradation of Cav-1, which is a major pathway of its downregulation during cell anoikis. Furthermore, addition of hydrogen peroxide exogenously to the cells inhibited Cav-1 downregulation by preventing the formation of Cav-1-ubiquitin complex, supporting the inhibitory role of endogenous hydrogen peroxide in Cav-1 degradation during cell detachment. Together, these results indicate a novel role of hydrogen peroxide as an endogenous suppressor of cell anoikis through its stabilizing effect on Cav-1.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Cell Physiology
Volume300
Issue number2
DOIs
StatePublished - Feb 2011
Externally publishedYes

Fingerprint

Anoikis
Caveolin 1
Non-Small Cell Lung Carcinoma
Hydrogen Peroxide
Down-Regulation
Reactive Oxygen Species
Acetylcysteine
Catalase
Caveolins
Neoplasm Metastasis
Ubiquitination
Ubiquitin
Hydroxyl Radical
Neoplasms

Keywords

  • Detachment
  • Metastasis
  • Reactive oxygen species

ASJC Scopus subject areas

  • Cell Biology
  • Physiology

Cite this

Hydrogen peroxide inhibits non-small cell lung cancer cell anoikis through the inhibition of caveolin-1 degradation. / Rungtabnapa, Pimuma; Nimmannit, Ubonthip; Halim, Hasseri; Rojanasakul, Yon; Chanvorachote, Pithi.

In: American Journal of Physiology - Cell Physiology, Vol. 300, No. 2, 02.2011.

Research output: Contribution to journalArticle

Rungtabnapa, Pimuma ; Nimmannit, Ubonthip ; Halim, Hasseri ; Rojanasakul, Yon ; Chanvorachote, Pithi. / Hydrogen peroxide inhibits non-small cell lung cancer cell anoikis through the inhibition of caveolin-1 degradation. In: American Journal of Physiology - Cell Physiology. 2011 ; Vol. 300, No. 2.
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