Preprint Article Version 1 This version is not peer-reviewed

24-Methylenecycloartanyl Ferulate Induces PPAR-γ2 Mediated Regulation of Angiogenesis-Related Genes and Inhibits Akt/mTOR Signaling

Version 1 : Received: 16 July 2018 / Approved: 17 July 2018 / Online: 17 July 2018 (09:10:14 CEST)

How to cite: Kim, J.B.; Lee, G.K.; Kim, H.; Kim, H.W.; Jang, H.H.; Yang, Y.M.; Lee, S.H.; Lee, S.H.; Park, J.H. 24-Methylenecycloartanyl Ferulate Induces PPAR-γ2 Mediated Regulation of Angiogenesis-Related Genes and Inhibits Akt/mTOR Signaling. Preprints 2018, 2018070297 (doi: 10.20944/preprints201807.0297.v1). Kim, J.B.; Lee, G.K.; Kim, H.; Kim, H.W.; Jang, H.H.; Yang, Y.M.; Lee, S.H.; Lee, S.H.; Park, J.H. 24-Methylenecycloartanyl Ferulate Induces PPAR-γ2 Mediated Regulation of Angiogenesis-Related Genes and Inhibits Akt/mTOR Signaling. Preprints 2018, 2018070297 (doi: 10.20944/preprints201807.0297.v1).

Abstract

We investigated the effect and molecular mechanism of 24-MCF-induced PPAR-γ2 on angiogenesis-related genes in MCF7 cells. cDNA microarray, semi-quantitative reverse transcription (RT)-PCR, and western blotting revealed that 24-MCF mediated the expression of genes related to angiogenesis in MCF-7 cells. Luciferase reporter assay demonstrated that promoter activation of the LIF gene, an anti-angiogenesis factor, was increased upon PPAR-γ2 overexpression and 24-MCF treatment, whereas activation of HoxA7 and VEGF promoters, known pro-angiogenesis factors, decreased upon PPAR-γ2 overexpression and 24-MCF treatment. We identified PPAR-response elements (PPRE) located in the VEGF (-913 to +1), HoxA7 (-1107 to +1), and LIF promoter regions (-9032 to -8403). VEGF promoter activity was abolished by mutation of the PPRE motif. Treatment with 24-MCF inhibited expression of VEGF and inhibited the Akt/mTOR pathway. Treatment with 24-MCF also decreased VEGF secretion in MCF7 cells and PMA-stimulated tube formation in HUVECs. Our findings suggest that 24-MCF induces PPAR-γ2-mediated regulation of anti-angiogenesis via PPRE motifs in VEGF, HoxA7, and LIF promoters or upstream regions. Furthermore, 24-MCF treatment inhibits angiogenesis by blocking VEGF secretion.

Subject Areas

24-methylenecycloartanyl ferulate, angiogenesis, PPAR-γ2, PPRE, Akt/mTOR, HoxA7, VEGF, LIF, HUVEC

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