The Cytotoxic Effects of Geranylgeranylacetone Are Attenuated in the High-Glucose Condition

Geranylgeranylacetone (GGA) has been used as an antiulcer drug and also is known as inducer of heat shock protein 70 that has cytoprotective effects especially in hyperglycemic condition. In contrast, cytotoxicity of GGA has also been reported. Some studies have reported that GGA suppresses cell growth and induces apoptosis in cell models of human leukemia, ovarian carcinoma, and colon cancer in vitro. Therefore, the aim of this study was to determine whether GGA can have a cytotoxic effect on a human cervical cancer cell line (HeLa), human colorectal adenocarcinoma cells (Caco-2), and human embryonic kidney cells 293 (HEK) in normal-glucose and high-glucose environments (NG and HG, respectively). The results showed that 100 mu M GGA inhibited proliferation of HeLa cells only in NG environment despite inhibiting proliferation of Caco-2 and HEK cells regardless of glucose concentration. Cell viability assay revealed that GGA decreased viability of HeLa, Caco-2, and HEK cells only in NG environment. Flow cytometric analyses revealed that the type of cell death was a combination of necrosis and apoptosis. Our study revealed that difference in cytotoxicity of GGA is influenced by glucose condition. The cytotoxic effects of GGA are attenuated in the HG condition. Since both cytotoxic and cytoprotective effects are reported about GGA, further research is needed about the mechanism of the cytotoxic effects.