RRR-gamma-tocopherol induces human breast cancer cells to undergo apoptosis via death receptor 5 (DR5)-mediated apoptotic signaling.
Goal of this study was to investigate the pro-apoptotic properties of RRR-gamma-tocopherol (gammaT) in human breast cancer cells. gammaT was shown to induce cancer cells but not normal cells to undergo apoptosis, sensitize cancer cells to Tumor necrosis factor-Related Apoptosis-Inducing Ligand (TRAIL)-induced apoptosis, and increase death receptor 5 (DR5) mRNA, protein and cell surface expression. Knockdown of DR5 attenuated gammaT-induced apoptosis. Investigations of post-receptor signaling showed: caspase-8, Bid and Bax activation, increases in mitochondria permeability, cytochrome c release and caspase-9 activation. Thus, gammaT is a potent pro-apoptotic agent for human breast cancer cells inducing apoptosis via activation of DR5-mediated apoptotic pathway.
Yu
Weiping
W
School of Biological Sciences, University of Texas at Austin, Austin, TX, USA.
Park
Sook-Kyung
SK
Jia
Li
L
Tiwary
Richa
R
Scott
Wenjun W
WW
Li
Jing
J
Wang
Pei
P
Simmons-Menchaca
Marla
M
Sanders
Bob G
BG
Kline
Kimberly
K
D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects*; D051023:BH3 Interacting Domain Death Agonist Protein / Q000378:metabolism; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D053181:Caspase 8 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D045744:Cell Line, Tumor; D045304:Cytochromes c / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D005260:Female; D006801:Humans; D042361:Mammary Glands, Human / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects / Q000201:enzymology; D051336:Mitochondrial Membranes / Q000187:drug effects; D010539:Permeability; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000378:metabolism; D013997:Time Factors; D014815:Vitamins / Q000494:pharmacology* / Q000627:therapeutic use; D024502:alpha-Tocopherol / Q000494:pharmacology; D051028:bcl-2-Associated X Protein / Q000378:metabolism; D024504:gamma-Tocopherol / Q000494:pharmacology* / Q000627:therapeutic use
D000970:Antineoplastic Agents; C494826:BAX protein, human; D051023:BH3 Interacting Domain Death Agonist Protein; C494814:BID protein, human; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D053221:TNF-Related Apoptosis-Inducing Ligand; D014815:Vitamins; D051028:bcl-2-Associated X Protein; D024504:gamma-Tocopherol; D045304:Cytochromes c; C505530:CASP8 protein, human; D053181:Caspase 8; D053453:Caspase 9; D024502:alpha-Tocopherol