J Pharm Pharmacogn Res 2(Suppl. 1): S30, 2014
Special supplement with the abstract book of LATINFARMA 2013
C 012: EPIGENETIC REGULATION OF BREAST CANCER METASTASIS BY STEROIDAL LACTONE WITHAFERIN A
Szarcvel Szic K1, Scherf D2, Beck IM3, Bracke M3, De Meyer T4, Gerhauser C2, Vanden Berghe W.1
Because a vast majority of cancer patients succumb metastatic disease interfering with metastatic cascade remains one of the main challenges in cancer therapy. This dangerous, yet very inefficient process includes several discrete steps: local invasion, intravasation (or dissemination in lymph nodes or body cavities), circulation and survival, extravasation, growth at distinct sites and angiogenesis, all of which occur in a context of tumour promoting microenvironment. It is now becoming apparent that these cell-microenvironment interactions are highly susceptible to epigenetic regulation, both by internal and external cues.
Here we show that several essential components of metastasis, including urokinase plasminogen activator (PLAU), ADAM8 metallopeptidase, and tumour promoting cytokine TNFSF12 are regulated epigenetically by DNA methylation in breast cancer as revealed by 450K IlluminaBeadChipArray and EpiTyper Mass Array. Moreover, Withaferin A, a natural compound derived from Withania somnifera decreases breast cancer invasion by increasing methylation of these genes leading to lowered gene expression as revealed by qPCR.