CdSe quantum dots induce apoptosis in human neuroblastoma cells via mitochondrial-dependent pathways and inhibition of survival signals.
Quantum dots (QDs) may be useful as novel luminescent markers, but their cytotoxicity has not been fully investigated. In this report, we demonstrate that CdSe-core QDs can induce apoptotic biochemical changes, including JNK activation, loss of mitochondrial membrane potential, mitochondrial release of cytochrome c and activation of caspase-9 and caspase-3 in the IMR-32 human neuroblastoma cell line. Importantly, treatment of IMR-32 cells with CdSe-core QD triggered an increase in reactive oxygen species (ROS) and inhibited survival-related signaling events, such as decreased Ras and Raf-1 protein expression and decreased ERK activation. These apoptotic biochemical changes were not detected in cells treated with ZnS-coated CdSe QDs. Collectively, these results demonstrate that CdSe-core QD treatment of IMR-32 cells induced JNK activation and mitochondrial-dependent apoptotic processes while inhibiting Ras-->ERK survival signaling and that a ZnS coating could effectively reduce QD cytotoxicity.
Chan
Wen-Hsiung
WH
Department of Bioscience Technology, Center for Nanotechnology, Chung Yuan Christian University, Chung Li, Taiwan. whchan@cycu.edu.tw
Shiao
Nion-Heng
NH
Lu
Pin-Zhen
PZ
D017209:Apoptosis / Q000187:drug effects*; D019187:Cadmium Compounds / Q000633:toxicity*; D053148:Caspase 3 / Q000502:physiology; D053453:Caspase 9 / Q000502:physiology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D018841:HSP90 Heat-Shock Proteins / Q000096:biosynthesis; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000502:physiology; D008928:Mitochondria / Q000502:physiology*; D009447:Neuroblastoma / Q000473:pathology*; D045663:Quantum Dots; D017382:Reactive Oxygen Species; D018036:Selenium Compounds / Q000633:toxicity*; D015398:Signal Transduction / Q000187:drug effects
D019187:Cadmium Compounds; D018841:HSP90 Heat-Shock Proteins; D017382:Reactive Oxygen Species; D018036:Selenium Compounds; C058667:cadmium selenide; D048031:JNK Mitogen-Activated Protein Kinases; D053148:Caspase 3; D053453:Caspase 9