PPARgamma-mediated ALDH1A3 suppression exerts anti-proliferative effects in lung cancer by inducing lipid peroxidation.
J Recept Signal Transduct Res
; 38(3): 191-197, 2018 Jun.
Article
em En
| MEDLINE
| ID: mdl-29873276
ABSTRACT
CONTEXT The metabolic function of peroxisome proliferator-activated receptor gamma (PPARγ) in lung cancer remains unclear. OBJECTIVES:
To determine the relationship of PPARγ on ALDH1A3-induced lipid peroxidation to inhibit lung cancer cell growth. MATERIALS ANDMETHODS:
In silico analysis using microarray dataset was performed to screen the positive correlation between PPARγ and all ALDH isoforms. NUBIscan software and ChIP assay were used to identify the binding sites (BSs) of PPARγ on ALDH1A3 promoter. The expression of ALDH1A3 under thiazolidinedione (TZD) treatment was evaluated by QPCR and Western Blot in HBEC and H1993 cell lines. Upon treatment of TZD, colony formation assay was used to check cell growth inhibition and 4-hydroxy-2-nonenal (4HNE) production as lipid peroxidation marker was determined by Western Blot in PPARγ positive cell H1993 and PPARγ negative cell H1299.RESULTS:
Compared to other ALDH isoforms, ALDH1A3 showed the highest positive correlation to PPARγ expression. ALDH1A3 upregulated PPARγ expression while PPARγ activation suppressed ALDH1A3. Among 2 potential screened PPARγ response elements, BS 1 and 2 in the promoter of ALDH1A3 gene, PPARγ bound directly to BS2. Ligand activation of PPARγ suppressed mRNA and protein expression of ALDH1A3. Growth inhibition was observed in H1993 (PPARγ positive cell) treated with PPARγ activator and ALDH inhibitor compared to H1299 (PPARγ negative cell). PPARγ activation increased 4HNE which is known to be suppressed by ALDH1A3.CONCLUSIONS:
ALDH1A3 suppression could be one of PPARγ tumor suppressive function. This study provides a better understanding of the role of PPARγ in lung cancer.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
PPAR gama
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Proliferação de Células
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Aldeído Oxirredutases
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Neoplasias Pulmonares
Limite:
Humans
Idioma:
En
Revista:
J Recept Signal Transduct Res
Assunto da revista:
BIOQUIMICA
/
FISIOLOGIA
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
Coréia do Sul