期刊
MOLECULAR NUTRITION & FOOD RESEARCH
卷 56, 期 6, 页码 923-934出版社
WILEY
DOI: 10.1002/mnfr.201200027
关键词
Apoptosis; Breast cancer; Docosahexaenoic acid; ER stress; Vitamin E
资金
- Clayton Foundation for Research
Scope: Docosahexaenoic acid (DHA) has been shown to exhibit anticancer actions in vitro and in vivo in a variety of cancers. Here, we investigated the role for DHA in inducing apoptosis in triple-negative breast cancer (TNBC) and studied the mechanisms of action. Methods and results: DHA induces apoptosis as detected by Annexin V-FITC/PI assay as well as induces cleavage of caspase-8 and -9, endoplasmic reticulum stress (ERS), and elevated levels of death receptor-5 (DR5) protein expression as detected by western blot assays. Chemical inhibitors of caspase-8 and -9 and small interfering RNAs (siRNAs) show DHA to induce ERS/CHOP/DR5-mediated caspase-8 and -9 dependent apoptosis. Furthermore, DHA induces elevated cellular levels of reactive oxygen species (ROS) and antioxidant; RRR-alpha-tocopherol (alpha T) blocked DHA-induced apoptotic events. In contrast to the antagonistic impact of alpha T, gamma-tocotrienol (gamma T3) was demonstrated to cooperate with DHA in inducing apoptotic events in TNBC cells. Conclusion: Data, for the first time, demonstrate that DHA induces apoptosis in TNBC cells via activation of ERS/CHOP/DR5-mediated caspase-8 and -9 dependent pro-apoptotic events, and that different forms of vitamin E exhibit distinct effects on DHA-induced apoptosis; namely, inhibition by alpha T and enhancement by gamma T3.
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