Licochalcone A enhances geldanamycin-induced apoptosis through reactive oxygen species-mediated caspase activation.
OBJECTIVE
Geldanamycin and licochalcone A induce apoptosis in cancer cells. However, whether the combination of geldanamycin and licochalcone A-induced apoptosis in epithelial ovarian cancer cells is mediated by the formation of reactive oxygen species, leading to the activation of apoptotic caspase, has not been studied.


METHODS
Using the human epithelial ovarian carcinoma cell lines OVCAR-3 and SK-OV-3, we investigated the promoting effect of licochalcone A on geldanamycin-induced apoptosis.


RESULTS
Geldanamycin induced changes in apoptosis-related protein levels, loss of the mitochondrial transmembrane potential, release of cytochrome c, activation of caspases, cleavage of PARP-1, formation of reactive oxygen species and depletion of glutathione (GSH). Licochalcone A enhanced geldanamycin-induced apoptosis-related protein activation, formation of reactive oxygen species, caspase activation and cell death. The combined effect was inhibited by the addition of oxidant scavengers.


CONCLUSIONS
Licochalcone A may potentiate the apoptotic effect of geldanamycin on ovarian carcinoma cell lines by the activation of the caspase-8- and Bid-dependent pathways and the mitochondria-mediated apoptotic pathway. The apoptosis-promoting effect of licochalcone A may be mediated by its stimulatory action on the formation of reactive oxygen species and the depletion of GSH, which results in the activation of caspases.
Department of Pharmacology, College of Medicine, Chung-Ang University, Seoul, South Korea.
Yun Jeong
YJ
Kim
Eun Byul
EB
Jung
Soon Chul
SC
Myung
Wonyong
W
Kim
Chung Soo
CS
Lee
D000970:Antineoplastic Agents / Q000008:administration & dosage*; D000971:Antineoplastic Combined Chemotherapy Protocols; D017209:Apoptosis / Q000187:drug effects; D016227:Benzoquinones / Q000008:administration & dosage*; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D047188:Chalcones / Q000008:administration & dosage*; D045304:Cytochromes c / Q000378:metabolism; D004357:Drug Synergism; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D047029:Lactams, Macrocyclic / Q000008:administration & dosage*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage*; D017382:Reactive Oxygen Species / Q000378:metabolism
D000970:Antineoplastic Agents; D016227:Benzoquinones; D047188:Chalcones; D047029:Lactams, Macrocyclic; D047428:Protein Kinase Inhibitors; D017382:Reactive Oxygen Species; D045304:Cytochromes c; D020169:Caspases; D005978:Glutathione; C070840:licochalcone A; C001277:geldanamycin