Docosahexaenoic acid induces apoptosis in MCF-7 cells in vitro and in vivo via reactive oxygen species formation and caspase 8 activation
- Docosahexaenoic acid induces apoptosis in MCF-7 cells in vitro and in vivo via reactive oxygen species formation and caspase 8 activation
- 강기성; Pan Wang; Yamabe Noriko; Fukui Masayuki; Jay Taylor; Bao Ting Zhu
- DHA; MCF-7; Apoptosis; Caspase-8; ROS
- Issue Date
- PLOS ONE
- VOL 5, NO 4, e10296-1-e10296-13
- Background: The present study sought to further investigate the in vitro and in vivo anticancer effects of a representative
omega-3 fatty acid, docosahexaenoic acid (DHA), with a focus on assessing the induction of oxidative stress and apoptosis
as an important mechanism for its anticancer actions.
Methodology/Principal Findings: In vitro studies showed that DHA strongly reduces the viability and DNA synthesis of
MCF-7 human breast cancer cells in culture, and also promotes cell death via apoptosis. Mechanistically, accumulation of
reactive oxygen species and activation of caspase 8 contribute critically to the induction of apoptotic cell death. Copresence
of antioxidants or selective inhibition or knockdown of caspase 8 each effectively abrogates the cytotoxic effect of
DHA. Using athymic nude mice as an in vivo model, we found that feeding animals the 5% fish oil-supplemented diet for 6
weeks significantly reduces the growth of MCF-7 human breast cancer cells in vivo through inhibition of cancer cell
proliferation as well as promotion of cell death. Using 3-nitrotyrosine as a parameter, we confirmed that the fish oilsupplemented
diet significantly increases oxidative stress in tumor cells in vivo. Analysis of fatty acid content in plasma and
tissues showed that feeding animals a 5% fish oil diet increases the levels of DHA and eicosapentaenoic acid in both normal
and tumorous mammary tissues by 329% and 300%, respectively.
Conclusions/Significance: DHA can strongly induce apoptosis in human MCF-7 breast cancer cells both in vitro and in vivo.
The induction of apoptosis in these cells is selectively mediated via caspase 8 activation. These observations call for further
studies to assess the effectiveness of fish oil as a dietary supplement in the prevention and treatment of human breast
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