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Licochalcone A enhances geldanamycin-induced apoptosis through reactive oxygen species-mediated caspase activation
Yun Jeong Kim1, Eun Byul Jung, Soon Chul Myung
1Department of Pharmacology, College of Medicine, Chung-Ang University, Seoul, South Korea.
Background And Purpose:
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.
Experimental Approach:
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.
Insights
Licochalcone A enhances geldanamycin-induced apoptosis in ovarian cancer cells by increasing reactive oxygen species and activating caspases. This combination therapy offers a potential strategy for treating ovarian carcinoma.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Geldanamycin and licochalcone A are known to induce apoptosis in cancer cells.
- The combined effect of geldanamycin and licochalcone A on epithelial ovarian cancer cells, specifically regarding reactive oxygen species (ROS) and caspase activation, was previously unstudied.
Purpose of the Study:
- To investigate the synergistic effect of licochalcone A on geldanamycin-induced apoptosis in human epithelial ovarian carcinoma cell lines.
- To elucidate the role of reactive oxygen species (ROS) and caspase activation in the combined apoptotic mechanism.
Main Methods:
- Utilized human epithelial ovarian carcinoma cell lines (OVCAR-3 and SK-OV-3).
- Assessed apoptosis-related protein levels, mitochondrial transmembrane potential, cytochrome c release, caspase activation, PARP-1 cleavage, ROS formation, and glutathione (GSH) levels.
- Investigated the effect of oxidant scavengers on the combined treatment.
Main Results:
- Geldanamycin alone induced apoptosis markers, including ROS formation and GSH depletion.
- Licochalcone A significantly enhanced geldanamycin-induced apoptosis, characterized by increased ROS production, caspase activation, and cell death.
- The pro-apoptotic effects of the combination were attenuated by oxidant scavengers.
Conclusions:
- Licochalcone A potentiates geldanamycin-induced apoptosis in ovarian cancer cells via caspase-8, Bid-dependent, and mitochondria-mediated pathways.
- The apoptosis-promoting action of licochalcone A is linked to increased ROS generation and GSH depletion, leading to caspase activation.
Related Concept Videos
01:31The Intrinsic Apoptotic Pathway
01:24Caspases