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5-(4-Chlorophenyl)-1-(4-methoxyphenyl)-3-trifluoromethylpyrazole acts in a reactive oxygen species-dependent manner to suppress human lung cancer growth

5-(4-Chlorophenyl)-1-(4-methoxyphenyl)-3-trifluoromethylpyrazole acts in a reactive oxygen... Purpose: 5-(4-Chlorophenyl)-1-(4-methoxyphenyl)-3-trifluoromethylpyrazole (SC-560) is a structural analog of celecoxib. Recent studies suggested that SC-560 inhibits the in vivo proliferation of colon and breast cancer cells to an extent similar to that observed in celecoxib, and that SC-560 exerts their growth inhibitory effects in a cyclooxygenase-independent manner. Methods: In the current study, we sought to investigate the mechanism by which SC-560 inhibits the growth of human lung cancer cells. Results: SC-560 more potently inhibited the growth of human A549, H460, and H358 lung cancer cell lines compared with that of human BEAS-2B normal bronchial epithelial cells. SC-560-induced growth inhibition was mainly due to the induction of cell-cycle arrest at the G1 phase without apoptosis induction. SC-560 rapidly and dose-dependently induced the generation of reactive oxygen species (ROS), followed by accumulation of cells at the G1 phase. Antioxidant pretreatment blocked the cell-cycle arrest and growth inhibition induced by SC-560. Combination treatment with other ROS-inducing agents such as α-tocopheryl succinate (TOS) augmented cellular response against SC-560, leading to synergistic apoptosis induction and growth suppression. Our data also showed that the apoptosis induced by combination treatment with SC-560 and TOS was mediated through ROS-dependent caspase activation. Conclusion: Collectively, our results demonstrate that SC-560 acts in a ROS-dependent manner to induce growth suppression in human lung cancer cells. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Journal of Cancer Research and Clinical Oncology Springer Journals

5-(4-Chlorophenyl)-1-(4-methoxyphenyl)-3-trifluoromethylpyrazole acts in a reactive oxygen species-dependent manner to suppress human lung cancer growth

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References (43)

Publisher
Springer Journals
Copyright
Copyright © 2005 by Springer-Verlag
Subject
Medicine & Public Health; Hematology; Internal Medicine ; Cancer Research ; Oncology
ISSN
0171-5216
eISSN
1432-1335
DOI
10.1007/s00432-005-0063-7
pmid
16362334
Publisher site
See Article on Publisher Site

Abstract

Purpose: 5-(4-Chlorophenyl)-1-(4-methoxyphenyl)-3-trifluoromethylpyrazole (SC-560) is a structural analog of celecoxib. Recent studies suggested that SC-560 inhibits the in vivo proliferation of colon and breast cancer cells to an extent similar to that observed in celecoxib, and that SC-560 exerts their growth inhibitory effects in a cyclooxygenase-independent manner. Methods: In the current study, we sought to investigate the mechanism by which SC-560 inhibits the growth of human lung cancer cells. Results: SC-560 more potently inhibited the growth of human A549, H460, and H358 lung cancer cell lines compared with that of human BEAS-2B normal bronchial epithelial cells. SC-560-induced growth inhibition was mainly due to the induction of cell-cycle arrest at the G1 phase without apoptosis induction. SC-560 rapidly and dose-dependently induced the generation of reactive oxygen species (ROS), followed by accumulation of cells at the G1 phase. Antioxidant pretreatment blocked the cell-cycle arrest and growth inhibition induced by SC-560. Combination treatment with other ROS-inducing agents such as α-tocopheryl succinate (TOS) augmented cellular response against SC-560, leading to synergistic apoptosis induction and growth suppression. Our data also showed that the apoptosis induced by combination treatment with SC-560 and TOS was mediated through ROS-dependent caspase activation. Conclusion: Collectively, our results demonstrate that SC-560 acts in a ROS-dependent manner to induce growth suppression in human lung cancer cells.

Journal

Journal of Cancer Research and Clinical Oncology – Springer Journals

Published: Dec 13, 2005

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