A Succinate Ether Derivative of Tocotrienol Enhances Dickkopf-1 Gene Expression through Epigenetic Alterations in Malignant Mesothelioma Cells

Pharmacology
Ayami SatoTomohiro Yano

Abstract

Wnt signaling plays an essential role in tumor cell growth, including the development of malignant mesothelioma (MM). Epigenetic silencing of negative Wnt regulators leading to constitutive Wnt signaling has been observed in various cancers and warrants further attention. We have reported that a succinate ether derivative of α-tocotrienol (T3E) has potent cytotoxic effects in MM cells. Thus, in this study, we investigated whether the anti-MM effect of T3E could be mediated via the epigenetic alteration of the Wnt antagonist gene, Dickkopf-1 (DKK1). WST-1 and cell analyzers were employed to analyze the effects of T3E on cell viability and apoptosis of human MM cell lines (H2452, H28). Real-time PCR and Western blot were performed to evaluate the expression at mRNA and protein levels. Methylation status and epigenetic modifications of DKK1's promoter regions after T3E treatment in MM cells were studied using methylation-specific PCR and Chromatin immunoprecipitation. Small interfering RNA-mediated knockdown -(siRNA), and specific inhibitors, were used to validate DKK1 as a target of T3E. T3E markedly impaired MM cell viability, increased the expression of phosphorylated-JNK and DKK1 and suppressed cyclin D, a downstream target ge...Continue Reading

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Citations

Nov 20, 2019·Bioscience, Biotechnology, and Biochemistry·Kakeru KohnoTomohiro Yano
Jun 20, 2020·Nanomedicine·Gabriel Silva Marques BorgesLucas Antônio Miranda Ferreira
Jun 4, 2019·Biological & Pharmaceutical Bulletin·Ayami SatoTomohiro Yano
May 21, 2019·International Journal of Cancer. Journal International Du Cancer·Vladan MilosevicChiara Riganti
Feb 23, 2021·Frontiers in Molecular Biosciences·Shuang-Xi LiZhi-Yong Guo

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