Dihydro-alpha-lipoic acid has more potent cytotoxicity than alpha-lipoic acid.
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.
Yamasaki
Masao
M
Department of Biochemistry and Applied Biosciences, Faculty of Agriculture, University of Miyazaki, 1-1 Gakuenkibanadai-nishi, Miyazaki, 889-2192, Japan.
Kawabe
Akiko
A
Nishimoto
Kentaro
K
Madhyastha
Harishkumar
H
Sakakibara
Yoichi
Y
Suiko
Masahito
M
Okamoto
Takeaki
T
Suda
Taiji
T
Uehira
Kenzo
K
Nishiyama
Kazuo
K
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*
D017304:Annexin A5; D011419:Propidium; D008063:Thioctic Acid; C015144:dihydrolipoic acid; D053148:Caspase 3