Distinct roles of different forms of vitamin E in DHA-induced apoptosis in triple-negative breast cancer cells.

Abstract

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-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.

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 αT and enhancement by γT3.

• Authors: Ailian Xiong, Weiping Yu, Richa Tiwary, Bob G Sanders, Kimberly Kline
• Journal: Molecular nutrition & food research (Mol Nutr Food Res) Vol. 56 Issue 6 Pg. 923-34 (Jun 2012) ISSN: 1613-4133 [Electronic] Germany
• PMID: 22707267 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Chemical References

• Antineoplastic Agents
• Antioxidants
• Caspase Inhibitors
• Chromans
• Cysteine Proteinase Inhibitors
• DDIT3 protein, human
• Neoplasm Proteins
• RNA, Messenger
• RNA, Small Interfering
• Reactive Oxygen Species
• Receptors, TNF-Related Apoptosis-Inducing Ligand
• Vitamin E
• Transcription Factor CHOP
• Docosahexaenoic Acids
• plastochromanol 8
• Caspases, Initiator
• alpha-Tocopherol

Topics

• Antineoplastic Agents (agonists, antagonists & inhibitors, metabolism, pharmacology)
• Antioxidants (metabolism, pharmacology)
• Apoptosis (drug effects)
• Breast Neoplasms (drug therapy, metabolism)
• Caspase Inhibitors
• Caspases, Initiator (metabolism)
• Cell Line, Tumor
• Chromans (pharmacology)
• Cysteine Proteinase Inhibitors (pharmacology)
• Docosahexaenoic Acids (agonists, antagonists & inhibitors, metabolism)
• Endoplasmic Reticulum Stress (drug effects)
• Female
• Gene Expression Regulation, Neoplastic (drug effects)
• Humans
• Neoplasm Proteins (antagonists & inhibitors, genetics, metabolism)
• RNA Interference
• RNA, Messenger (metabolism)
• RNA, Small Interfering
• Reactive Oxygen Species (antagonists & inhibitors, metabolism)
• Receptors, TNF-Related Apoptosis-Inducing Ligand (antagonists & inhibitors, genetics, metabolism)
• Transcription Factor CHOP (antagonists & inhibitors, genetics, metabolism)
• Vitamin E (analogs & derivatives, metabolism, pharmacology)
• alpha-Tocopherol (metabolism)