Direct reaction between shikonin and thiols induces apoptosis in HL60 cells.
Shikonin (beta-alkannin), a naphthoquinone compound, was found to induce apoptotic features such as chromatin condensation, DNA fragmentation, and activation of caspase 3 in HL60 cells. The mechanism was examined in terms of oxidative stress in the cells. Exposure of the cells to shikonin greatly reduced the total thiols, protein thiols, and glutathione levels, however, lipid peroxide levels were enhanced. The depletion of thiol levels in the cells was thus thought to induce lipid peroxidation and DNA fragmentation. An electron spin resonance study revealed that shikonin reacts directly with glutathione and other oxidative stress-relevant compounds in the lysate of HL60 cells. Pretreatment of such cells with N-acetylcysteine before shikonin treatment completely inhibited the DNA fragmentation. From these results, it was proposed that the chemical reaction between shikonin and cellular thiols such as glutathione and protein thiols induces apoptosis in HL60 cells.
Gao
Dayuan
D
Department of Analytical and Bioinorganic Chemistry, Kyoto Pharmaceutical University, Japan.
Hiromura
Makoto
M
Yasui
Hiroyuki
H
Sakurai
Hiromu
H
D000111:Acetylcysteine / Q000494:pharmacology; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D053938:DNA Fragmentation / Q000187:drug effects; D004789:Enzyme Activation; D018922:HL-60 Cells / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D008054:Lipid Peroxides / Q000378:metabolism; D009285:Naphthoquinones / Q000494:pharmacology*; D013438:Sulfhydryl Compounds / Q000378:metabolism*
D000972:Antineoplastic Agents, Phytogenic; D008054:Lipid Peroxides; D009285:Naphthoquinones; D013438:Sulfhydryl Compounds; C016101:shikonin; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases; D000111:Acetylcysteine