δ- and γ-tocotrienols induce classical ultrastructural apoptotic changes in human T lymphoblastic leukemic cells.
Tocotrienols are isomers of the vitamin E family, which have been reported to exert cytotoxic effects in various cancer cells. Although there have been some reports on the effects of tocotrienols in leukemic cells, ultrastructural evidence of tocotrienol-induced apoptotic cell death in leukemic cells is lacking. The present study investigated the effects of three isomers of tocotrienols (alpha, delta, and gamma) on a human T lymphoblastic leukemic cell line (CEM-SS). Cell viability assays showed that all three isomers had cytotoxic effects (p < 0.05) on CEM-SS cells with delta-tocotrienol being the most potent. Transmission electron microscopy showed that the cytotoxic effects by delta- and gamma-tocotrienols were through the induction of an apoptotic pathway as demonstrated by the classical ultrastructural apoptotic changes characterized by peripheral nuclear chromatin condensation and nuclear fragmentation. These findings were confirmed biochemically by the demonstration of phosphatidylserine externalization via flow cytometry analysis. This is the first study showing classical ultrastructural apoptotic changes induced by delta- and gamma-tocotrienols in human T lymphoblastic leukemic cells.
Division of Human Biology, School of Medical and Health Sciences, International Medical University, Malaysia No 126, Jalan Jalil Perkasa 19, Bukit Jalil, 57000 Kuala Lumpur, Malaysia. mail: rebecca_wong@imu.edu.my
Rebecca S Y
RS
Wong
Ammu K
AK
Radhakrishnan
Tengku Azmi Tengku
TA
Ibrahim
Soon-Keng
SK
Cheong
D017209:Apoptosis; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000648:ultrastructure; D002470:Cell Survival / Q000187:drug effects; D002839:Chromans / Q000633:toxicity*; D002843:Chromatin / Q000648:ultrastructure; D006801:Humans; D046529:Microscopy, Electron, Transmission; D013601:T-Lymphocytes / Q000187:drug effects* / Q000502:physiology / Q000648:ultrastructure; D024508:Tocotrienols; D014810:Vitamin E / Q000031:analogs & derivatives* / Q000633:toxicity
D002839:Chromans; D002843:Chromatin; D024508:Tocotrienols; D014810:Vitamin E; C082097:tocotrienol, delta; C013649:plastochromanol 8; C082032:tocotrienol, alpha