Gamma-tocotrienol acts as a BH3 mimetic to induce apoptosis in neuroblastoma SH-SY5Y cells

Jen Kit Tan, Sue Mian Then, Musalmah Mazlan, Raja Noor Zaliha Raja Abdul Rahman, A. Rahman A. Jamal, Wan Zurinah Wan Ngah

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Bcl-2 family proteins are crucial regulators of apoptosis. Both pro- and antiapoptotic members exist, and overexpression of the latter facilitates evasion of apoptosis in many cancer types. Bcl-2 homology domain 3 (BH3) mimetics are small molecule inhibitors of antiapoptotic Bcl-2 family members, and these inhibitors are promising anticancer agents. In this study, we report that gamma-tocotrienol (γT3), an isomer of vitamin E, can inhibit Bcl-2 to induce apoptosis. We demonstrate that γT3 induces cell death in human neuroblastoma SH-SY5Y cells by depolarising the mitochondrial membrane potential, enabling release of cytochrome c to the cytosol and increasing the activities of caspases-9 and -3. Treatment of cells with inhibitors of Bax or caspase-9 attenuated the cell death induced by γT3. Simulated docking analysis suggested that γT3 binds at the hydrophobic groove of Bcl-2, while a binding assay showed that γT3 competed with a fluorescent probe to bind at the hydrophobic groove. Our data suggest that γT3 mimics the action of BH3-only protein by binding to the hydrophobic groove of Bcl-2 and inducing apoptosis via the intrinsic pathway in a Bax- and caspase-9-dependent manner.

Original languageEnglish
Pages (from-to)28-37
Number of pages10
JournalJournal of Nutritional Biochemistry
Volume31
DOIs
Publication statusPublished - 1 May 2016

Fingerprint

Neuroblastoma
Caspase 9
Apoptosis
Cell death
Cell Death
Mitochondrial Membrane Potential
Cytochromes c
Vitamin E
Fluorescent Dyes
Protein Binding
Caspase 3
Isomers
Antineoplastic Agents
Cytosol
Assays
Proteins
Cells
Membranes
Molecules
plastochromanol 8

Keywords

  • Apoptosis
  • Bcl-2
  • BH3 mimetic
  • Gamma-tocotrienol
  • Neuroblastoma
  • Vitamin E

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry
  • Molecular Biology
  • Endocrinology, Diabetes and Metabolism
  • Nutrition and Dietetics

Cite this

Gamma-tocotrienol acts as a BH3 mimetic to induce apoptosis in neuroblastoma SH-SY5Y cells. / Tan, Jen Kit; Then, Sue Mian; Mazlan, Musalmah; Raja Abdul Rahman, Raja Noor Zaliha; A. Jamal, A. Rahman; Wan Ngah, Wan Zurinah.

In: Journal of Nutritional Biochemistry, Vol. 31, 01.05.2016, p. 28-37.

Research output: Contribution to journalArticle

Tan, Jen Kit ; Then, Sue Mian ; Mazlan, Musalmah ; Raja Abdul Rahman, Raja Noor Zaliha ; A. Jamal, A. Rahman ; Wan Ngah, Wan Zurinah. / Gamma-tocotrienol acts as a BH3 mimetic to induce apoptosis in neuroblastoma SH-SY5Y cells. In: Journal of Nutritional Biochemistry. 2016 ; Vol. 31. pp. 28-37.
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