@Article{096504017X14941825760362,
AUTHOR = {Lian Zheng, Zhen-Jie Guan, Wen-Ting Pan, Tian-Feng Du, Yu-Jia Zhai, Jia Guo},
TITLE = {Tanshinone Suppresses Arecoline-Induced Epithelial–Mesenchymal Transition  in Oral Submucous Fibrosis by Epigenetically Reactivating the p53 Pathway},
JOURNAL = {Oncology Research},
VOLUME = {26},
YEAR = {2018},
NUMBER = {3},
PAGES = {483--494},
URL = {http://www.techscience.com/or/v26n3/56660},
ISSN = {1555-3906},
ABSTRACT = {Oral submucous fibrosis (OSF) induced by chewing of the areca nut has been considered to be a precancerous lesion with a high probability of developing oral squamous cell carcinoma. Tanshinone (TSN) is the main 
component extracted from Salvia miltiorrhiza, a traditional Chinese medicine, which was found to have diverse 
pharmacological effects, such as anti-inflammatory and antitumor. In the current study, we aimed to identify 
the inhibitory effects and the underlying mechanism of TSN on OSF progress. We found that treatment with 
TSN inhibited the arecoline-mediated proliferation of primary human oral mucosal fibroblasts and reversed 
the promotive effects of arecoline on the EMT process. By RNA deep sequencing, we screened two possible 
targets for TSN: LSD1 and p53. We confirmed that p53 is much lower in OSF than in normal mucous tissues. In 
addition, p53 and its downstream molecules were decreased by arecoline treatment in oral mucosal fibroblasts, 
which was reversed by treatment with TSN in a dose-dependent manner. Our results also revealed that arecoline stimulation resulted in hypermethylation of the promoter of <i>TP53</i> and subsequent downregulation of p53 
levels, which was reversed by TSN. Furthermore, we identified that LSD1 could epigenetically activate <i>TP53</i>
by recruiting H3K27me1 and H3K4m2 to its promoter. Our findings provide new insights into the mechanism 
by which TSN influences arecoline-induced OSF and rationale for the development of clinical intervention 
strategies for OSF and even oral squamous cell carcinoma.},
DOI = {10.3727/096504017X14941825760362}
}