Epigenetic modification of Huntingtin associated protein‐1 by bioactive natural components as a strategy for the prevention and treatment of breast cancer

Abstract

The objectives of this study were to determine if Huntingtin associated protein‐1 (HAP1) could serve as a functional target for breast cancer (BRCA) and if bioactive natural components that modulate HAP1 expression and function may have preventive and/or therapeutic activities against BRCA. Searching for novel targets for effective prevention and therapy remains the to priority in BRCA research. The role of HAP in BRCA has not been investigated. The DNA promoter of HAP1 gene has CpG islands, suggesting that HAP1 expression could be epigenetically modified. Our in vitro studies showed that, compared with the normal breast epithelial cells, human BRCA cell lines had dramatically reduced HAP1 gene expression associated with hypermethylation of its DNA promoter. The results were also confirmed in human samples of cancerous and normal breast tissues. Gain‐of‐function assays showed that overexpression of HAP1 inhibited growth rates of BRCA cell lines. Several bioactive dietary and botanical components inhibited the growth of BRCA cells associated with up‐regulation of HAP1 gene expression and DNA promoter hypomethylation, with tanshinone IIA the most potent component. These results suggest that HAP1 could serve as a functional target for BRCA, and epigenetic modification of HAP1 expression may provide a novel approach to identify bioactive dietary and natural components for prevention and treatment of BRCA.