title: Induction of apoptosis by γ-tocotrienol in human cancer cell lines and leukemic blasts from patients: dependency on Bid, cytochrome c, and caspase pathway.
abstract: Tocotrienols (Toc3) have been suggested to possess anticancer effects besides antioxidant and antiinflammatory effects. Previous studies have demonstrated that Toc3 induce apoptosis in epithelial carcinoma. However, the effects of Toc3 on malignant hematopoietic cells have not yet been thoroughly investigated. We investigated Toc3-induced apoptosis in human hematological cancer cell lines. α-, δ-, and γ-Toc3 induced concentration-dependent apoptosis, and γ-Toc3 demonstrated more effective induction than the other Toc3 derivatives in HL-60 cells. γ-Toc3 may have induced apoptosis by activation of the caspase cascade, cytochrome c (Cyt.c) release, Bid cleavage, and mitochondorial membrane depolarization in HL-60, NB-4, Raji, and SY-5Y cells. Furthermore, 10-30 μM γ-Toc3 showed cytotoxicity for leukemic cells from various patients regardless of lymphoblastic, myeloblastic, or relapsed leukemia, but the cytotoxic effect was weak in normal mononuclear cells, interestingly. γ-Toc3 may have a role in cancer prevention and potential for treating hematological malignancies.
authors.affiliation: Department of Pediatrics, Osaka Medical College, Takatsuki, Osaka, Japan. ped031@poh.osaka-med.ac.jp
authors.forename: Akiko
authors.initials: A
authors.lastname: Inoue
authors.forename: Kimitaka
authors.initials: K
authors.lastname: Takitani
authors.forename: Maki
authors.initials: M
authors.lastname: Koh
authors.forename: Chihiro
authors.initials: C
authors.lastname: Kawakami
authors.forename: Tomoko
authors.initials: T
authors.lastname: Kuno
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Tamai
mesh_terms: D000293:Adolescent; D000972:Antineoplastic Agents, Phytogenic / Q000378:metabolism*; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism*; D051023:BH3 Interacting Domain Death Agonist Protein / Q000378:metabolism; D001854:Bone Marrow Cells / Q000378:metabolism / Q000473:pathology; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000473:pathology; D049109:Cell Proliferation; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D002839:Chromans / Q000378:metabolism*; D045304:Cytochromes c / Q000378:metabolism; D053938:DNA Fragmentation; D005260:Female; D019337:Hematologic Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control; D006801:Humans; D007223:Infant; D007938:Leukemia / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control; D008297:Male; D053078:Membrane Potential, Mitochondrial; D008928:Mitochondria / Q000378:metabolism* / Q000473:pathology; D009363:Neoplasm Proteins / Q000378:metabolism; D014810:Vitamin E / Q000031:analogs & derivatives* / Q000378:metabolism
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D051017:Apoptosis Regulatory Proteins; D051023:BH3 Interacting Domain Death Agonist Protein; C494814:BID protein, human; D002839:Chromans; D009363:Neoplasm Proteins; D014810:Vitamin E; C013649:plastochromanol 8; D045304:Cytochromes c; D020169:Caspases