title: Dihydro-alpha-lipoic acid has more potent cytotoxicity than alpha-lipoic acid.
abstract: Alpha-lipoic acid has been shown to possess cancer-cell-killing activity via activation of the apoptosis pathway. In this study, the cytotoxic activities of alpha-lipoic and dihydro-alpha-lipoic acid were compared in HL-60 cells. The cell-killing activity of dihydro-alpha-lipoic acid was higher than that of alpha-lipoic acid. Both alpha-lipoic and dihydro-alpha-lipoic acid induced caspase-3 cleavage and internucleosomal DNA fragmentation in treated cells. On the other hand, apparent necrotic or late-stage apoptotic cell populations could be detected in dihydro-alpha-lipoic acid cells but not in those treated with alpha-lipoic acid. Moreover, dihydro-alpha-lipoic acid, but not alpha-lipoic acid, induced marked mitochondrial permeability transition. Antioxidants could not prevent dihydro-alpha-lipoic- or alpha-lipoic-acid-induced cell death. In addition, dihydro-alpha-lipoic and alpha-lipoic acid did not up-regulate cellular reactive oxygen level. These results indicated that dihydro-alpha-lipoic acid exerts more potent cytotoxicity than alpha-lipoic acid through different cytotoxic actions.
authors.affiliation: Department of Biochemistry and Applied Biosciences, Faculty of Agriculture, University of Miyazaki, 1-1 Gakuenkibanadai-nishi, Miyazaki, 889-2192, Japan.
authors.forename: Masao
authors.initials: M
authors.lastname: Yamasaki
authors.forename: Akiko
authors.initials: A
authors.lastname: Kawabe
authors.forename: Kentaro
authors.initials: K
authors.lastname: Nishimoto
authors.forename: Harishkumar
authors.initials: H
authors.lastname: Madhyastha
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Sakakibara
authors.forename: Masahito
authors.initials: M
authors.lastname: Suiko
authors.forename: Takeaki
authors.initials: T
authors.lastname: Okamoto
authors.forename: Taiji
authors.initials: T
authors.lastname: Suda
authors.forename: Kenzo
authors.initials: K
authors.lastname: Uehira
authors.forename: Kazuo
authors.initials: K
authors.lastname: Nishiyama
mesh_terms: D017304:Annexin A5 / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D053938:DNA Fragmentation / Q000187:drug effects; D005434:Flow Cytometry; D018922:HL-60 Cells; D006801:Humans; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism; D008928:Mitochondria / Q000187:drug effects / Q000201:enzymology; D010084:Oxidation-Reduction / Q000187:drug effects; D010539:Permeability / Q000187:drug effects; D011419:Propidium / Q000378:metabolism; D008063:Thioctic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology*
chemical_list: D017304:Annexin A5; D011419:Propidium; D008063:Thioctic Acid; C015144:dihydrolipoic acid; D053148:Caspase 3