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Delta- and Gamma-Tocotrienols Induce Classical Ultrastructural Apoptotic Changes in Human T Lymphoblastic Leukemic Cells

Published online by Cambridge University Press:  16 April 2012

Rebecca S.Y. Wong ,
Ammu K. Radhakrishnan ,
Tengku Azmi Tengku Ibrahim  and
Soon-Keng Cheong
Rebecca S.Y. Wong*
Affiliation:
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
Ammu K. Radhakrishnan
Affiliation:
Division of Pathology, School of Medical and Health Sciences, International Medical University, Malaysia No 126, Jalan Jalil Perkasa 19, Bukit Jalil, 57000 Kuala Lumpur, Malaysia
Tengku Azmi Tengku Ibrahim
Affiliation:
Microscopy Unit, Institute of Bioscience, University Putra Malaysia, Serdang 43100 Selangor, Malaysia
Soon-Keng Cheong
Affiliation:
Faculty of Medicine and Health Sciences, University Tunku Abdul Rahman, Malaysia. Jalan Sungai Long, Bandar Sungai Long, Cheras 43000 Kajang, Selangor, Malaysia
*
Corresponding author. E-mail: [email protected]; [email protected]
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Abstract

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.

Keywords

tocotrienolsT lymphoblastic leukemiaphosphatidylserine externalizationperipheral chromatin condensationnuclear fragmentationapoptosis
Type
Biological Applications
Information
Microscopy and Microanalysis , Volume 18 , Issue 3 , June 2012 , pp. 462 - 469
Copyright
Copyright © Microscopy Society of America 2012

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