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Luteolin promotes apoptotic cell death via upregulation of Nrf2 expression by DNA demethylase and the interaction of Nrf2 with p53 in human colon cancer cells.
Kang, Kyoung Ah; Piao, Mei Jing; Hyun, Yu Jae; Zhen, Ao Xuan; Cho, Suk Ju; Ahn, Mee Jung; Yi, Joo Mi; Hyun, Jin Won.
Afiliación
  • Kang KA; Jeju National University School of Medicine and Jeju Research Center for Natural Medicine, Jeju, 63243, Republic of Korea.
  • Piao MJ; Jeju National University School of Medicine and Jeju Research Center for Natural Medicine, Jeju, 63243, Republic of Korea.
  • Hyun YJ; Jeju National University School of Medicine and Jeju Research Center for Natural Medicine, Jeju, 63243, Republic of Korea.
  • Zhen AX; Jeju National University School of Medicine and Jeju Research Center for Natural Medicine, Jeju, 63243, Republic of Korea.
  • Cho SJ; Jeju National University School of Medicine and Jeju Research Center for Natural Medicine, Jeju, 63243, Republic of Korea.
  • Ahn MJ; Laboratory of Veterinary Anatomy, College of Veterinary Medicine, Jeju National University, Jeju, 63243, Republic of Korea.
  • Yi JM; Department of Microbiology and Immunology, Inje University College of Medicine, Busan, 47392, Republic of Korea.
  • Hyun JW; Jeju National University School of Medicine and Jeju Research Center for Natural Medicine, Jeju, 63243, Republic of Korea. jinwonh@jejunu.ac.kr.
Exp Mol Med ; 51(4): 1-14, 2019 04 15.
Article en En | MEDLINE | ID: mdl-30988303
Luteolin, a dietary flavone, modulates various signaling pathways involved in carcinogenesis. In this study, we investigated the molecular mechanism that underlies the apoptotic effects of luteolin mediated by DNA demethylation of the nuclear factor erythroid 2-related factor 2 (Nrf2) promoter and the interaction of Nrf2 and p53, a tumor suppressor, in human colon cancer cells. Luteolin increased the expression of apoptosis-related proteins and antioxidant enzymes. In DNA methylation, luteolin inhibited the expression of DNA methyltransferases, a transcription repressor, and increased the expression and activity of ten-eleven translocation (TET) DNA demethylases, a transcription activator. Methyl-specific polymerase chain reaction and bisulfite genomic sequencing indicated that luteolin decreased the methylation of the Nrf2 promoter region, which corresponded to the increased mRNA expression of Nrf2. In addition, luteolin increased TET1 binding to the Nrf2 promoter, as determined using a chromatin immunoprecipitation (ChIP) assay. TET1 knockdown decreased the percentages of luteolin-treated cells in sub-G1 phase and cells with fragmented nuclei. Furthermore, complex formation between p53 and Nrf2 was involved in the apoptotic effects of luteolin. These results provide insight into the mechanism that underlies the anticancer effects of luteolin on colon cancer, which involve the upregulation of Nrf2 and its interaction with the tumor suppressor.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proteína p53 Supresora de Tumor / Apoptosis / Neoplasias del Colon / Luteolina / Factor 2 Relacionado con NF-E2 Límite: Humans Idioma: En Revista: Exp Mol Med Asunto de la revista: BIOLOGIA MOLECULAR / BIOQUIMICA Año: 2019 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proteína p53 Supresora de Tumor / Apoptosis / Neoplasias del Colon / Luteolina / Factor 2 Relacionado con NF-E2 Límite: Humans Idioma: En Revista: Exp Mol Med Asunto de la revista: BIOLOGIA MOLECULAR / BIOQUIMICA Año: 2019 Tipo del documento: Article Pais de publicación: Estados Unidos