Physcion 8-O-β-glucopyranoside suppresses the metastasis of breast cancer in vitro and in vivo by modulating DNMT1

Background: The present study is designed to explore the metastasis-inhibitory effect of physcion 8-O-beta-glucopyranoside (PG) in human breast cancer, and the mechanisms underlying its role in tumor metastasis. Methods: Both in vitro and in vivo studies were conducted. Cell migration and invasion were analyzed by transwell assay. The translocation of beta-catenin from the nucleus to cytoplasm membrane was demonstrated by immunofluorescent staining. The expression of signaling molecules was determined by Western blot or qRT-PCR. Results: The present study showed that PG suppressed the migration, invasion, and EMT of breast cancer cells MDA-MB-231 in a dose-dependent manner. The results also revealed that impairment of the metastatic potential caused by PG was associated with the activation of AMPK and downregulation of both DNMT1 and Sp1. Moreover, the data from the in vivo model also supported the in vitro findings, which showed that inhibition of metastasis by PG was associated with the downregulation of DNMT1 and Spl as well as increased level of phosphorylated AMPK. Conclusion: The present study showed that PG could suppress the metastasis of breast cancer, which highlighted a novel pharmacological application of this compound. Given the aggressive properties of breast cancer, the current study suggests that PG can serve as a safe therapeutic agent for suppressing breast cancer metastasis, although additional data is necessitated. (C) 2016 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Sp. z o.o. All rights reserved.