C 012: EPIGENETIC REGULATION OF BREAST CANCER METASTASIS BY STEROIDAL LACTONE WITHAFERIN A

J Pharm Pharmacogn Res 2(Suppl. 1): S30, 2014

Special supplement with the abstract book of LATINFARMA 2013

Conference

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

1Laboratory of Protein Chemistry, Proteomics and Epigenetic Signalling, Department of Biomedical Sciences, University of Antwerp (UA), Universiteitsplein 1, Campus DrieEiken, 2610, Wilrijk, Belgium.
2Cancer Chemoprevention, Epigenomics and Cancer Risk Factors, German Cancer Research Center (DKFZ), ImNeuenheimer Feld 280, 69120, Heidelberg, Germany.
3Laboratory for Experimental Cancer Research, Department of Radiation Therapy & Experimental Cancer Research, De Pintelaan 185, Building 1P7, Ghent University Hospital, B-9000, Gent, Belgium.
4Department of Mathematical Modelling, Ghent University, Ghent, Belgium.
Abstract

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.