Breast and colon cancer cells were assessed for effects of genipin on 18F-FDG uptake. T47D breast cancer cells were further evaluated for time-dependent and dose-dependent effects on 18F-FDG uptake, lactate release, oxygen consumption rate (OCR), reactive oxygen species (ROS) production, and mitochondrial membrane potential. The effects of UCP2 knockdown were evaluated using specific siRNA.
Cancer cells displayed significant reductions in 18F-FDG uptake by genipin. T47D cells showed the greatest reduction to 32.6 ± 1.0% of controls by 250 μM genipin. The effect occurred rapidly, reaching a plateau by 1 h that lasted up to 24 h. The effect was dose-dependent with a half-inhibitory concentration of 60.8 μM. An accompanying decrease in lactate release was consistent with reduced glycolytic flux. OCR was significantly decreased by genipin to 82.2 ± 11.4% of controls, and ROS generation was increased to 156.7 ± 16.0%. These effects were largely reproduced by UCP2 knockdown with specific siRNA.
Genipin decreased cancer cell 18F-FDG uptake by reducing both glycolytic flux and mitochondrial oxidative respiration. This effect appeared to occur by blocking the ability of UCP2 to dissipate energy and restrict ROS production through proton leakage.