The apoptotic process of human bladder carcinoma T24 cells induced by retinoid.
Breakdown of the cytoskeletal network and redistribution of cytoplasmic organelles are early events of programmed cell death. Previous studies showed that retinoic acid induces programmed cell death in many tumor cell lines and that cytokeratins, particularly cytokeratin 18, are affected in the early events of apoptosis. In this study, patterns of cytoplasmic intermediate filaments (cytokeratin 18), actin filaments, and microtubules, as well as Bax and Bcl-2 proteins in human bladder carcinoma T24 cells were examined before and after retinoic acid treatment by immunocytochemistry and conventional electron microscopy. Our results demonstrate that the redistribution of Bax and Bcl-2 proteins in the subcellular compartment of T24 cells is correlated with reorganization of the cytoplasmic intermediate filament network and that cytokeratins are cleaved by caspases, as revealed by the M30 antibody which recognizes a specific caspase cleavage site within cytokeratin 18. The cytoskeletal architectures of microtubules are not significantly affected in the early apoptotic process, from our observations. We suggest that the breakdown in the intermediate filament network associated with the aggregation of mitochondria and lysosome may be a crucial event in the apoptotic process and that aggregation of cytoplasmic Bax may accelerate apoptotic death.
Chien
Chung-Liang
CL
Department of Anatomy and Cell Biology, College of Medicine, National Taiwan University, Taipei, Taiwan. clc@ha.mc.ntu.edu.tw
Chen
Tung-Wei
TW
Lin
Yi-Shan
YS
Lu
Kuo-Shyan
KS
D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D006801:Humans; D007633:Keratins / Q000032:analysis; D012176:Retinoids / Q000494:pharmacology*; D001749:Urinary Bladder Neoplasms / Q000473:pathology* / Q000648:ultrastructure
D012176:Retinoids; D007633:Keratins