Beta-carotene and cigarette smoke condensate regulate heme oxygenase-1 and its repressor factor Bach1: relationship with cell growth

Simona Serini, Diego Curro', Gabriella Calviello, Cesare Mancuso, Paola Palozza, Kazuhiko Igarashi

Risultato della ricerca: Contributo in rivistaArticolo in rivista

Abstract

It has been reported that beta-carotene is able to increase lung cancer risk in chronic smokers, but the mechanism for this association remains unknown. In this paper, we report the first evidence that beta-carotene, combined with cigarette smoke condensate (TAR), regulated heme oxygenase-1 (HO-1) via its transcriptional factor Bach1 and modulated cell growth. We found that both immortalized rat fibroblasts (RAT-1) and human lung cancer cells (Mv1Lu) exposed to TAR (25 microg/ml), exhibited an initial (6 h) induction of HO-1 followed by a late (24 h) repression due to the activation of Bach1. Heme oxygenase-1 repression was much more consistent when TAR was administered in combination with beta-carotene (1 microM) for 24 h; at this concentration the carotenoid per se did not have any effect on HO-1. Interestingly, the HO-1 repression following TAR plus beta-carotene treatment caused a re-synchronization of RAT-1 cell-cycle with a significant increase in the S-phase, and this was probably due to the decreased intracellular levels of carbon monoxide and bilirubin, both of which have anti-proliferative effects. The role of HO-1 repression in increasing cell growth was also confirmed in Mv1Lu cells by the ¿knock down¿ of the Bach1 gene, thus demonstrating as HO-1 repression is a conserved mechanism by which cells can react to oxidative stress.
Lingua originaleEnglish
pagine (da-a)1069-1080
Numero di pagine12
RivistaANTIOXIDANTS & REDOX SIGNALING
Stato di pubblicazionePubblicato - 2006

Keywords

  • Bach-1
  • beta-carotene
  • cell growth
  • cigarette tar
  • heme oxygenase 1
  • oxidative stress

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