Dietary omega-3 fatty acid intake impacts peripheral blood DNA methylation -anti-inflammatory effects and individual variability in a pilot study.

Omega-3 or n-3 polyunsaturated fatty acids (PUFAs) are widely studied for health benefits that may relate to anti-inflammatory activity. However, mechanisms mediating an anti-inflammatory response to n-3 PUFA intake are not fully understood. Of interest is the emerging role of fatty acids to impact DNA methylation (DNAm) and thereby modulate mediating inflammatory processes. In this pilot study, we investigated the impact of n-3 PUFA intake on DNAm in inflammation-related signaling pathways in peripheral blood mononuclear cells (PBMCs) of women at high risk of breast cancer. PBMCs of women at high risk of breast cancer (n=10) were obtained at baseline and after 6 months of n-3 PUFA (5 g/d EPA+DHA dose arm) intake in a previously reported dose finding trial. DNA methylation of PBMCs was assayed by reduced representation bisulfite sequencing (RRBS) to obtain genome-wide methylation profiles at the single nucleotide level. We examined the impact of n-3 PUFA on genome-wide DNAm and focused upon a set of candidate genes associated with inflammation signaling pathways and breast cancer. We identified 24,842 differentially methylated CpGs (DMCs) in gene promoters of 5507 genes showing significant enrichment for hypermethylation in both the candidate gene and genome-wide analyses. Pathway analysis identified significantly hypermethylated signaling networks after n-3 PUFA treatment, such as the Toll-like Receptor inflammatory pathway. The DNAm pattern in individuals and the response to n-3 PUFA intake are heterogeneous. PBMC DNAm profiling suggests a mechanism whereby n-3 PUFAs may impact inflammatory cascades associated with disease processes including carcinogenesis.

Effects of total glycosides from Baishouwu on human breast and prostate cancer cell proliferation.

Baishouwu (Cynanchum Auriculalum Royle ex Wight), a traditional Chinese herbal medicine, is used as a traditional anti-aging remedy in China. Previous studies suggested Baishouwu has multiple pharmacological actions. In this study, the total glycosides extracted from Baishouwu (CA/TG) were evaluated for its potential anti-tumor activity and mechanism on several human breast and prostate cancer cell lines. In [3H] thymidine incorporation assay. CA/TG inhibited the proliferation of cancer cells in a dose-dependent fashion. It also displayed anti-androgen activity on androgen sensitive cell line assessed by reporter gene assay. The morphological examination of CA/TG treated cells revealed overall shrinkage of nucleus, chromatin condensation and small nuclear fragments by DAPI staining, the characteristic pattern of DNA ladders were observed in cells exposed to CA/TG, indicating the involvement of apoptosis in its action. These results suggested that the CA/TG has preferred cytotoxicity against the cancer cells, and the action was due to its ability of preventing cell proliferation and inducing apoptosis.