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J Thorac Cardiovasc Surg 2000;119:795-803
© 2000 The American Association for Thoracic Surgery

GENERAL THORACIC SURGERY

PACLITAXEL-INDUCED APOPTOSIS IN NON–SMALL CELL LUNG CANCER CELL LINES IS ASSOCIATED WITH INCREASED CASPASE-3 ACTIVITY

From the Section of Thoracic Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY^a; and Biological Therapeutics Laboratory^b and Divisions of Thoracic Surgery^c and Surgical Oncology,^d University of Pittsburgh Cancer Institute, Pittsburgh, Pa.

Supported by "Fondation pour la Recherche Medicale" (grant No. SE 000619-01) by the Division of Thoracic Surgery and the UPCI Biological Therapeutics Program (NCI-1POI CA 68067-01 and National Institutes of Health 1POI DE12321, both to M.T.L.).

Address for reprints: Tracey L. Weigel, MD, Section of Thoracic Surgery, Memorial Sloan-Kettering Cancer Center, 1275 York Ave, New York, NY 10021 (E-mail: weigelt{at}mskcc.org ).

Objective: Our objective was to determine whether paclitaxel-induced apoptosis in human lung cancer cells is Fas dependent.
Methods: Human lung cancer cell lines were evaluated for morphologic evidence of apoptosis, DNA fragmentation (TUNEL positivity), and caspase-3 activation after paclitaxel treatment. Human lung adenocarcinoma, squamous cell carcinoma, undifferentiated lung carcinoma, and bronchoalveolar carcinoma cell lines were each cultured in 10 µmol/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. TUNEL 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 from 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 significant). Apoptotic morphologic changes were inhibited in cells cultured in the presence of paclitaxel and Ac-DEVD-CHO, a caspase-3 inhibitor.
Conclusions: Paclitaxel induces apoptosis in lung cancer cell lines, as assessed by a consistent increase in caspase-3 activity, DNA laddering, and characteristic morphologic changes. Paclitaxel-induced apoptosis in human lung cancer cells is associated with caspase-3 activation but is not Fas dependent.

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