dimethyl sulfoxide promotes the multiple functions of the tumor suppressor hlj1 through activator protein-1 activation in nsclc cells二甲亚砜的多种功能促进肿瘤抑制hlj1通过激活蛋白1在nsclc细胞活化.pdfVIP

Dimethyl Sulfoxide Promotes the Multiple Functions of the Tumor Suppressor HLJ1 through Activator Protein-1 Activation in NSCLC Cells 1 2 2 1 1 2 Chi-Chung Wang *, Sheng-Yi Lin , Yi-Hua Lai , Ya-Jung Liu , Yuan-Lin Hsu , Jeremy J. W. Chen * 1 Graduate Institute of Basic Medicine, Fu Jen Catholic University, Taipei, Taiwan, 2 Institutes of Biomedical Sciences and Molecular Biology, National Chung-Hsing University, Taichung, Taiwan Abstract Background: Dimethyl sulfoxide (DMSO) is an amphipathic molecule that displays a diversity of antitumor activities. Previous studies have demonstrated that DMSO can modulate AP-1 activity and lead to cell cycle arrest at the G1 phase. HLJ1 is a newly identified tumor and invasion suppressor that inhibits tumorigenesis and cancer metastasis. Its transcriptional activity is regulated by the transcription factor AP-1. However, the effects of DMSO on HLJ1 are still unknown. In the present study, we investigate the antitumor effects of DMSO through HLJ1 induction and demonstrate the mechanisms involved. Methods and Findings: Low-HLJ1-expressing highly invasive CL1–5 lung adenocarcinoma cells were treated with various concentrations of DMSO. We found that DMSO can significantly inhibit cancer cell invasion, migration, proliferation, and colony formation capabilities through upregulation of HLJ1 in a concentration-dependent manner, whereas ethanol has no effect. In addition, the HLJ1 promoter and enhancer reporter assay revealed that DMSO transcriptionally upregulates HLJ1 expression through an AP-1 site within the HLJ1 enhancer. The AP-1 subfamily members JunD and JunB were significantly upregulated by DMSO in a con