Anticancer Activity of Protocatechualdehyde in Human Breast Cancer Cells

Protocatechualdehyde (PCA) is a natural polyphenol compound isolated from the root of the herb S. miltiorrhiza and barley tea plants. PCA possesses antiproliferative and pro-apoptotic properties in human colorectal cancer cells. However, the cellular mechanism has not been fully understood. beta-catenin and cyclin D1 are proto-oncogene that is over-expressed in many types of cancers and leads to cancer development. The present study was performed to elucidate the molecular mechanism by which PCA stimulates cell growth arrest and apoptosis in human breast cancer cells. PCA repressed cell proliferation and induced apoptosis in dose-dependent manner. PCA suppressed the expression of beta-catenin and cyclin D1 with no changes in mRNA levels. Inhibition of proteosomal degradation using MG-132 and Ada-(Ahx)(3)-(Leu)(3)-vinyl sulfone ameliorates PCA-induced downregulation of beta-catenin and cyclin D1. PCA treatment decreased the half-life of beta-catenin and cyclin D1. PCA-mediated beta-catenin downregulation depends on GSK3 beta. We further provide the evidence that PCA increased nuclear translocation of nuclear factor kappa-B (NF-kappa B) and the blockage of NF-kappa B using Bay11-7082 inhibited PCA-mediated beta-catenin downregulation. The current study demonstrates that PCA suppress beta-catenin expression through GSK3 beta- and NF-kappa B-mediated proteosomal degradation. In addition, PCA decreased cyclin D1 expression independent to beta-catenin through proteosomal degradation.