Enhanced hydroxychavicol-induced cytotoxic effects in glutathione-depleted HepG2 cells.
Hydroxychavicol (HC) is the major safrole urinary metabolite in rats and humans. The cytotoxic potential of HC in metabolically competent cells has yet to be studied. HC alone was slightly toxic to HepG2 cells. However, the cytotoxicity increased significantly (P<0.05) when HepG2 cells were pretreated with buthionine sulfoximine (BSO), suggesting that endogenous glutathione participates in HC-induced cytotoxicity. Addition of catalase or N-acetylcysteine prevented the BSO plus HC-mediated cytotoxicity. HC also increased 8-hydroxy-2'-deoxyguanosine formation and apoptosis in BSO-pretreated HepG2 cells and this increase could also be suppressed by catalase. These data suggest that BSO pretreatment enhanced HC-induced cytotoxic effects in HepG2 cells, which are related to oxidative DNA damage.
Chen
C L
CL
Institute of Pharmacology, National Yang-Ming University, Taipei, Taiwan.
Chi
C W
CW
Liu
T Y
TY
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000111:Acetylcysteine / Q000494:pharmacology; D000964:Antimetabolites, Antineoplastic; D017209:Apoptosis / Q000187:drug effects; D019328:Buthionine Sulfoximine / Q000494:pharmacology; D002374:Catalase / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects*; D004247:DNA / Q000378:metabolism; D053938:DNA Fragmentation / Q000187:drug effects; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004583:Electrons; D005054:Eugenol / Q000031:analogs & derivatives* / Q000378:metabolism; D016166:Free Radical Scavengers / Q000494:pharmacology; D005978:Glutathione / Q000378:metabolism*; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism; D009153:Mutagens; D018384:Oxidative Stress / Q000187:drug effects; D017382:Reactive Oxygen Species; D013997:Time Factors; D014407:Tumor Cells, Cultured
D000964:Antimetabolites, Antineoplastic; D016166:Free Radical Scavengers; D009153:Mutagens; D017382:Reactive Oxygen Species; C051268:2-hydroxychavicol; D005054:Eugenol; D019328:Buthionine Sulfoximine; D000080242:8-Hydroxy-2'-Deoxyguanosine; D004247:DNA; D002374:Catalase; D003849:Deoxyguanosine; D005978:Glutathione; D000111:Acetylcysteine