Paclitaxel-induced apoptosis in non-small cell lung cancer cell lines is associated with increased caspase-3 activity

Objective: Our objective was to determine whether paclitaxel-induced apopto sis in human lung cancer cells is Fas dependent. Methods: Human lung cancer cell lines were evaluated for morphologic eviden ce of apoptosis, DNA fragmentation (TUNEL positivity), and caspase-3 activa tion after paclitaxel treatment. Human lung adenocarcinoma, squamous cell c arcinoma, undifferentiated lung carcinoma, and bronchoalveolar carcinoma ce ll lines were each cultured in 10 mu moL/L paclitaxel, Results: After 24 hours of culture in paclitaxel, a 22% to 69% increase in the number of apoptotic cells was evident by means of methylene blue-azure A-eosin staining with characteristic blebbing and nuclear condensation. TUN EL assay also confirmed an increase of 19.9% to 73.0% of cells with nuclear fragmentation. Caspase-3 activity, assayed by Z-DEVD cleavage, increased f rom 20% to 215% (P < .05). ZB4, an antagonistic anti-Fas antibody, did not block paclitaxel induction of caspase-3 activity (155.8 vs 165.8 U, not sig nificant). Apoptotic morphologic changes were inhibited in cells cultured i n the presence of paclitaxel and Ac-DEVD-CHO, a caspase-3 inhibitor. Conclusions: Paclitaxel induces apoptosis in lung cancer cell lines, as ass essed by a consistent increase in caspase-3 activity, DNA laddering, and ch aracteristic morphologic changes. Paclitaxel-induced apoptosis in human lun g cancer cells is associated with caspase-3 activation but is not Fas depen dent.