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01-06-2007 | Original Article

Inhibition of NF-κB-mediated transcription and induction of apoptosis by melampolides and repandolides

Authors: Guoyi Ma, Shabana I. Khan, Gloria Benavides, Wolfgang Schühly, Nikolaus H. Fischer, Ikhlas A. Khan, David S. Pasco

Published in: Cancer Chemotherapy and Pharmacology | Issue 1/2007

Abstract

Purpose

Nuclear factor-κB (NF-κB) plays a crucial role in the regulation of inflammatory processes, cell proliferation, and apoptosis. Blocking NF-κB signaling may represent a therapeutic strategy in cancer and inflammation therapy. The aim of this study was to investigate the effects of sesquiterpenes isolated from Asteraceae, namely melampolides (enhydrin, tetraludin A) and repandolides (repandins A, B, D and E) on the activation of NF-κB, cell growth of cancer cells, cell cycle progression and apoptosis. In addition, their effects on the activity of cyclooxygenase-2 (COX-2) enzyme were also evaluated.

Methods

Cell-based reporter gene assay was conducted in SW1353 cells. COX-2 enzyme activity and cell growth inhibition was determined by enzyme immunoassay and MTT assay respectively. Cell cycle analysis was carried out by flow cytometry and apoptosis was observed by DAPI staining assay.

Results

In SW1353 cells, transcription mediated by NF-κB was inhibited by enhydrin, tetraludin A and repandins A, B, D and E, while Sp-1 mediated transcription was not affected. COX-2 enzyme activity was inhibited by enhydrin, repandin A and E, but not by tetraludin A, repandin B and D. These compounds were effective in inhibiting the growth of a panel of human tumor cell lines in a concentration-dependent manner. Cell cycle analysis and DAPI staining indicated cell cycle arrest in G₂/M phase and induction of apoptosis.

Conclusions

Enhydrin, tetraludin A and repandins A, B, D and E inhibited tumor cell growth and induced cell cycle arrest and apoptosis. These effects may be related to inhibition of NF-B activation.

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Title: Inhibition of NF-κB-mediated transcription and induction of apoptosis by melampolides and repandolides
Authors: Guoyi Ma
Shabana I. Khan
Gloria Benavides
Wolfgang Schühly
Nikolaus H. Fischer
Ikhlas A. Khan
David S. Pasco
Publication date: 01-06-2007
Publisher: Springer-Verlag
Published in: Cancer Chemotherapy and Pharmacology / Issue 1/2007
Print ISSN: 0344-5704
Electronic ISSN: 1432-0843
DOI: https://doi.org/10.1007/s00280-006-0344-0

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