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PPARgamma-mediated ALDH1A3 suppression exerts anti-proliferative effects in lung cancer by inducing lipid peroxidation.
Hua, Tuyen N M; Namkung, Jun; Phan, Ai N H; Vo, Vu T A; Kim, Min-Kyu; Jeong, Yangsik; Choi, Jong-Whan.
Afiliación
  • Hua TNM; a Department of Biochemistry, Wonju College of Medicine , Yonsei University , Wonju , South Korea.
  • Namkung J; b Department of Global Medical Science , Institute of Lifestyle Medicine, Nuclear Receptor Research Consortium, Mitohormesis Research Center, Wonju College of Medicine, Yonsei University , Wonju , South Korea.
  • Phan ANH; a Department of Biochemistry, Wonju College of Medicine , Yonsei University , Wonju , South Korea.
  • Vo VTA; a Department of Biochemistry, Wonju College of Medicine , Yonsei University , Wonju , South Korea.
  • Kim MK; b Department of Global Medical Science , Institute of Lifestyle Medicine, Nuclear Receptor Research Consortium, Mitohormesis Research Center, Wonju College of Medicine, Yonsei University , Wonju , South Korea.
  • Jeong Y; a Department of Biochemistry, Wonju College of Medicine , Yonsei University , Wonju , South Korea.
  • Choi JW; b Department of Global Medical Science , Institute of Lifestyle Medicine, Nuclear Receptor Research Consortium, Mitohormesis Research Center, Wonju College of Medicine, Yonsei University , Wonju , South Korea.
J Recept Signal Transduct Res ; 38(3): 191-197, 2018 Jun.
Article en En | MEDLINE | ID: mdl-29873276
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 AND METHODS: 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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: PPAR gamma / Proliferación Celular / Aldehído Oxidorreductasas / Neoplasias Pulmonares Límite: Humans Idioma: En Revista: J Recept Signal Transduct Res Asunto de la revista: BIOQUIMICA / FISIOLOGIA Año: 2018 Tipo del documento: Article País de afiliación: Corea del Sur Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: PPAR gamma / Proliferación Celular / Aldehído Oxidorreductasas / Neoplasias Pulmonares Límite: Humans Idioma: En Revista: J Recept Signal Transduct Res Asunto de la revista: BIOQUIMICA / FISIOLOGIA Año: 2018 Tipo del documento: Article País de afiliación: Corea del Sur Pais de publicación: Reino Unido