Taxol induces caspase-independent cytoplasmic vacuolization and cell death through endoplasmic reticulum (ER) swelling in ASTC-a-1 cells.
High concentration of taxol was found to induce programmed cell death (PCD) and cytoplasm vacuolization in human lung adenocarcinoma (ASTC-a-1) cells. To elucidate the relationship between the PCD and cytoplasm vacuolization, confocal fluorescence microscopy was performed on the cytoplasm vacuolization, endoplasmic reticulum (ER) and mitochondria swelling after taxol treatment in living cells. erRFP plasmid was used to probe the ER distribution, and SCAT3 plasmid was used to monitor the caspase-3 activation in living cells. Our results showed that taxol induced concentration-dependent and caspases-independent cytoplasm vacuolization and cell death through ER and mitochondria swelling. Live confocal imaging of ASTC-a-1 cells stably expressing SCAT3 further verified that taxol-induced cytoplasm vacuolization and cell death was caspase-3-independent. In conclusion, we found for the first time that taxol induces a paraptosis-like PCD in the ASTC-a-1 cells by cytoplasm vacuolization due to the swelling of both ER and mitochondria without activating the caspase enzymes.
MOE Key Laboratory of Laser Life Science & Institute of Laser Life Science, South China Normal University, Guangzhou, China. chentsh@scnu.edu.cn
Tong-sheng
TS
Chen
Xiao-ping
XP
Wang
Lei
L
Sun
Long-xiang
LX
Wang
Da
D
Xing
Martin
M
Mok
D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000502:physiology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003593:Cytoplasm / Q000187:drug effects* / Q000648:ultrastructure; D004721:Endoplasmic Reticulum / Q000187:drug effects*; D031541:Fluorescence Resonance Energy Transfer; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008933:Mitochondrial Swelling / Q000187:drug effects; D017239:Paclitaxel / Q000494:pharmacology*; D014617:Vacuoles / Q000187:drug effects*; D051020:bcl-X Protein / Q000032:analysis
D000972:Antineoplastic Agents, Phytogenic; C494811:BCL2L1 protein, human; D051020:bcl-X Protein; D053148:Caspase 3; D017239:Paclitaxel