Docosahexaenoic Acid Induces Apoptosis in MCF-7 Cells In Vitro and In Vivo via Reactive Oxygen Species Formation and Caspase 8 Activation

Ki Sung Kang; Pan Wang; Noriko Yamabe; Masayuki Fukui; Taylor Jay; Bao Ting Zhu

doi:10.1371/journal.pone.0010296

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Docosahexaenoic Acid Induces Apoptosis in MCF-7 Cells In Vitro and In Vivo via Reactive Oxygen Species Formation and Caspase 8 Activation

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Docosahexaenoic Acid Induces Apoptosis in MCF-7 Cells In Vitro and In Vivo via Reactive Oxygen Species Formation and Caspase 8 Activation

Ki Sung Kang, Pan Wang, Noriko Yamabe, Masayuki Fukui, Taylor Jay and Bao Ting Zhu

PloS one, Vol.5(4), p.e10296

04/22/2010

DOI: 10.1371/journal.pone.0010296

PMCID: PMC2858652

PMID: 20421971

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Abstract

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. Co-presence 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 oil-supplemented 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 cancer.

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Title: Subtitle: Docosahexaenoic Acid Induces Apoptosis in MCF-7 Cells In Vitro and In Vivo via Reactive Oxygen Species Formation and Caspase 8 Activation
Creators: Ki Sung Kang - University of Kansas
Pan Wang - University of Kansas
Noriko Yamabe - University of Kansas
Masayuki Fukui - University of Kansas
Taylor Jay - University of Kansas
Bao Ting Zhu - University of Kansas
Resource Type: Journal article
Publication Details: PloS one, Vol.5(4), p.e10296
DOI: 10.1371/journal.pone.0010296
PMID: 20421971
PMCID: PMC2858652
NLM abbreviation: PLoS One
ISSN: 1932-6203
eISSN: 1932-6203
Publisher: Public Library Science
Number of pages: 13
Grant note: P20RR021940 / National Center for Research Resources, NIH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Center for Research Resources (NCRR) ES015242 / National Institutes of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA
Language: English
Date published: 04/22/2010
Academic Unit: Iowa Neuroscience Institute; Neuroscience and Pharmacology
Record Identifier: 9985112882302771

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