The role of reactive oxygen species in regulation of human lung cancer cell anoikis by Caveolin-1

Abstract

anoikis or detachment-induced apoptosis plays an essential role in the regulation of cancer cell metastasis. caveolin-1 is a key protein involved in cancer metastasis but its role in anoikis and its regulation during cell detachment are unclear. this research reported that caveolin-1 plays a key role as a regulator of anoikis through a reactive oxygen species (ros)-dependent mechanism in human lung carcinoma h460 cells. during cell detachment, caveolin-1 is down-regulated, whereas reactive oxygen species generation is upregulated. in this research, treatments of specific reactive oxygen species scavengers showed that, hydrogen peroxide and hydroxyl radical are two key reactive oxygen species produced by cells during detachment. however, treatment of the cells with hydrogen peroxide scavengers, catalase and n-acetyl cysteine promoted caveolin-1 down-regulation and anoikis during cell detachment, indicated that only hydrogen peroxide plays a primary role in preventive cell anoikis by stabilizing caveolin-1 protein. further, the study demonstrated that, the mechanism of hydrogen peroxide in stabilizing caveolin-1 involved the inhibition of caveolin-1 degradation via ubiquitin proteasomal pathway. further, addition of subtoxic exogenous hydrogen peroxide could prevent caveolin-1- ubiquitin complex formation and subsequently inhibit caveolin-1 down regulation and cell anoikis. these results indicate a novel role of hydrogen peroxide as an endogenous suppressor of cell anoikis through its stabilizing effect on caveolin-1.