Preprint Article Version 1 This version is not peer-reviewed

Transcriptional Activation of Human GD3 Synthase (hST8Sia I) Gene In curcumin-Induced Autophagy in A549 Human Lung Carcinoma Cells

Version 1 : Received: 25 May 2018 / Approved: 25 May 2018 / Online: 25 May 2018 (11:12:02 CEST)

A peer-reviewed article of this Preprint also exists.

Lee, M.; Kim, K.-S.; Fukushi, A.; Kim, D.-H.; Kim, C.-H.; Lee, Y.-C. Transcriptional Activation of Human GD3 Synthase (hST8Sia I) Gene in Curcumin-Induced Autophagy in A549 Human Lung Carcinoma Cells. Int. J. Mol. Sci. 2018, 19, 1943. Lee, M.; Kim, K.-S.; Fukushi, A.; Kim, D.-H.; Kim, C.-H.; Lee, Y.-C. Transcriptional Activation of Human GD3 Synthase (hST8Sia I) Gene in Curcumin-Induced Autophagy in A549 Human Lung Carcinoma Cells. Int. J. Mol. Sci. 2018, 19, 1943.

Journal reference: Int. J. Mol. Sci. 2018, 19, 1943
DOI: 10.3390/ijms19071943

Abstract

Curcumin, a natural polyphenolic compound isolated from the plant Curcuma longa, is known to induce autophagy in various cancer cells, including lung cancer. In the present study, we also confirmed by LC3 immunofluorescence and immunoblotting analyses that curcumin triggers autophagy in human lung adenocarcinoma A549 cell line. In parallel with autophagy induction, gene expression of human GD3 synthase (hST8Sia I) responsible for ganglioside GD3 synthesis was markedly elevated in response to curcumin in A549 cells. To investigate transcriptional activation of hST8Sia I associated with autophagy formation in curcumin-treated A549 cells, functional characterization of the 5’-flanking region of the hST8Sia I gene was carried out using luciferase reporter assay system. Deletion analysis demonstrated that the -1146 to -646 region, which includes putative c-Ets-1, CREB, AP-1 and NF-κB binding sites, functions as the curcumin-responsive promoter of hST8Sia I in A549 cells. Site-directed mutagenesis and chromatin immunoprecipitation assay demonstrated that the NF-κB binding site at -731 to -722 was indispensable for the curcumin-induced hST8Sia I gene expression in A549 cells. Moreover, the transcriptional activation of hST8Sia I by curcumin A549 cells was strongly inhibited by compound C, an inhibitor of AMP-activated protein kinase (AMPK). These results suggest that curcumin controls hST8Sia I gene expression via AMPK signal pathway in A549 cells.

Subject Areas

autophagic cell death; curcumin; human GD3 synthase (hST8Sia I); A549 cells; transcriptional regulation

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