Taxol induces concentration-dependent apoptotic and paraptosis-like cell death in human lung adenocarcinoma (ASTC-a-1) cells.
Taxol (Paclitaxel) is an important natural product for the treatment of solid tumors such as ovarian, breast, non-small-cell lung tumors, and some head and neck carcinomas. Different concentrations of taxol trigger distinct effects on cell death forms. In present study, cell counting kit (CCK-8) assay, confocal fluorescence microscopy imaging, flow cytometry (FCM) and western blotting (WB) analysis were used to analyze the characteristics of cell death induced by low (35 nM) and high (70 microM) concentration of taxol respectively in human lung adenocarcinoma (ASTC-a-1) cells. Our results showed that low concentration of taxol induced cell death dominantly in apoptotic fashion associated with nuclear fragmentation, protein synthesis, phosphatidylserine (PS) externalization, G2/M cell cycle arrest, Bax translocation into mitochondria and caspase-3 activation, whereas high concentration of this drug induced significant cytoplasm vacuolization, mitochondria swelling and paraptosis-like cell death form without protein synthesis that is necessary for paraptosis. Although the mechanism of high concentration of taxol-induced paraptosis-like cell death has not been clear, this finding might have a potential implication for cancer therapy, especially for apoptosis-resistant cancer.
Guo
Wen-Jing
WJ
MOE Key Laboratory of Laser Life Science and Institute of Laser Life Science, South China Normal University, Guangzhou, China.
Chen
Tong-Sheng
TS
Wang
Xiao-Ping
XP
Chen
Rong
R
D000230:Adenocarcinoma / Q000378:metabolism; D000077192:Adenocarcinoma of Lung; D017302:Annexins / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D053148:Caspase 3 / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival; D003593:Cytoplasm / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D017239:Paclitaxel / Q000494:pharmacology*; D014617:Vacuoles / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism
D017302:Annexins; C494826:BAX protein, human; D051028:bcl-2-Associated X Protein; D053148:Caspase 3; D017239:Paclitaxel