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Research: SUN and COLLEAGUES,
Listed in Issue 168
Abstract
SUN and COLLEAGUES, Department of Pathology, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA investigated at the molecular level the mechanisms of n-3 polyunsaturated fatty acids' (n-3 PUFA) protection against breast cancer.
Background
Diets enriched in n-3 polyunsaturated fatty acids (n-3 PUFA) may protect against breast cancer but biochemical mechanisms are unclear. Our studies showed that the n-3 fatty acid docosahexaenoic acid (DHA) up-regulated syndecan-1 (SDC-1) in human breast cancer cells, and we tested the hypothesis that DHA-mediated up-regulation of SDC-1 induces apoptosis.
Methodology
DHA was delivered to MCF-7 cells by n-3 PUFA-enriched low-density lipoproteins (LDL) or by albumin in the presence or absence of SDC-1 small interfering RNA.
Results
The n-3 PUFA induced apoptosis, which was blocked by SDC-1 silencing. We also confirmed that SDC-1 up-regulation and apoptosis promotion by n-3 PUFA was mediated by peroxisome proliferator-activated receptor gamma (PPAR gamma). Using a luciferase gene driven by either a PPAR response element or a DR-1 site present in the SDC-1 promoter, reporter activities were enhanced by n-3 LDL, DHA, and PPAR gamma agonist, whereas activity of a luciferase gene placed downstream of a mutant DR-1 site was unresponsive. Cotransfection with dominant-negative PPAR gamma DNA eliminated the increase in luciferase activity.
Conclusion
These data provide strong evidence that SDC-1 is a molecular target of n-3 PUFA in human breast cancer cells through activation of PPAR gamma and that n-3 PUFA-induced apoptosis is mediated by SDC-1. This provides a novel mechanism for the chemopreventive effects of n-3 PUFA in breast cancer.
References
Sun H, Berquin IM, Owens RT, O'Flaherty JT and Edwards IJ. Peroxisome proliferator-activated receptor gamma-mediated up-regulation of syndecan-1 by n-3 fatty acids promotes apoptosis of human breast cancer cells. Cancer Research. 68 (8): 2912-9. Apr 15 2008.
Comment
This is important and impeccably performed research which details the mechanism of how n-3 PUFA induces apoptosis (cancer cell suicide).
