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

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 alpha-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.

• Authors: Eunmyong Lee, Moon-Kyung Choi, Hee-Jeong Youk, Cheol Hyeon Kim, Inn-Oc Han, Byung-Chul Yoo, Mi-Kyung Lee, Soo-Jeong Lim
• Journal: Journal of cancer research and clinical oncology (J Cancer Res Clin Oncol) Vol. 132 Issue 4 Pg. 223-33 (Apr 2006) ISSN: 0171-5216 [Print] Germany
• PMID: 16362334 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Drug Combinations
• Pyrazoles
• Reactive Oxygen Species
• SC 560
• Vitamin E
• Caspases
• Tocopherols

Topics

• Antineoplastic Agents (pharmacology)
• Apoptosis (drug effects)
• Caspases (metabolism)
• Cell Cycle (drug effects)
• Cell Proliferation (drug effects)
• Drug Combinations
• Drug Evaluation, Preclinical
• Drug Synergism
• Humans
• Lung Neoplasms (pathology)
• Models, Biological
• Pyrazoles (administration & dosage, pharmacology)
• Reactive Oxygen Species (pharmacology)
• Tocopherols
• Tumor Cells, Cultured
• Vitamin E (administration & dosage, analogs & derivatives)