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. β-catenin and cyclin D1 are proto-oncogene that is overexpressed 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 β-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 β-catenin and cyclin D1. PCA treatment decreased the half-life of β-catenin and cyclin D1. PCA-mediated β-catenin downregulation depends on GSK3β. We further provide the evidence that PCA increased nuclear translocation of nuclear factor kappa-B (NF-κB) and the blockage of NF-κB using Bay11-7082 inhibited PCA-mediated β-catenin downregulation. The current study demonstrates that PCA suppress β-catenin expression through GSK3β- and NF-κB-mediated proteosomal degradation. In addition, PCA decreased cyclin D1 expression independent to β-catenin through proteosomal degradation.
Department of Nutrition and Food Science, College of Agriculture and Natural Resources, University of Maryland , College Park, Maryland, USA .
Jieun
J
Choi
Xiaojing
X
Jiang
Jin Boo
JB
Jeong
Seong-Ho
SH
Lee
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001547:Benzaldehydes / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D002396:Catechols / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects; D005260:Female; D038362:Glycogen Synthase Kinase 3 / Q000235:genetics / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D000090063:Proto-Oncogene Mas; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism
D000970:Antineoplastic Agents; D001547:Benzaldehydes; D002396:Catechols; C000715470:MAS1 protein, human; D016328:NF-kappa B; D000090063:Proto-Oncogene Mas; D051176:beta Catenin; D019938:Cyclin D1; C005581:protocatechualdehyde; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; D038362:Glycogen Synthase Kinase 3
breast cancer; cyclin D1; protocatechualdehyde; β-catenin