These authors contributed equally to this work.
Distinct roles of different forms of vitamin E in DHA-induced apoptosis in triple-negative breast cancer cells
Article first published online: 18 JUN 2012
© 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Molecular Nutrition & Food Research
Volume 56, Issue 6, pages 923–934, June 2012
How to Cite
Xiong, A., Yu, W., Tiwary, R., Sanders, B. G. and Kline, K. (2012), Distinct roles of different forms of vitamin E in DHA-induced apoptosis in triple-negative breast cancer cells. Mol. Nutr. Food Res., 56: 923–934. doi: 10.1002/mnfr.201200027
- Issue published online: 18 JUN 2012
- Article first published online: 18 JUN 2012
- Manuscript Accepted: 22 MAR 2012
- Manuscript Revised: 19 MAR 2012
- Manuscript Received: 15 JAN 2012
- Breast cancer;
- Docosahexaenoic acid;
- ER stress;
- Vitamin E
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-α-tocopherol (αT) blocked DHA-induced apoptotic events. In contrast to the antagonistic impact of αT, gamma-tocotrienol (γT3) was demonstrated to cooperate with DHA in inducing apoptotic events in TNBC cells.
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 αT and enhancement by γT3.