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

• Published in: Cancer chemotherapy and pharmacology 2007-06, Vol.60 (1), p.35-43
• Main Authors: GUOYI MA, KHAN, Shabana I, BENAVIDES, Gloria, SCHUHIY, Wolfgang, FISCHER, Nikolaus H, KHAN, Ikhlas A, PASCO, David S
• Format: Article
• Language: English
• Subjects: Antineoplastic agents; Apoptosis; Asteraceae; Biological and medical sciences; Cancer; Cell activation; Cell cycle; Cell growth; Cell proliferation; Cyclooxygenase-2; Enzymatic activity; Enzyme activity; Enzyme immunoassay; Enzymes; Flow cytometry; Growth inhibition; Immunoassay; Inflammation; Medical sciences; NF-κB protein; Pharmacology. Drug treatments; Reporter gene; Sesquiterpenes; Staining; Transcription; Tumor cell lines; Tumors
• ISSN: 0344-5704; 1432-0843
• DOI: 10.1007/s00280-006-0344-0

PurposeNuclear 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.MethodsCell-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.ResultsIn 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.ConclusionsEnhydrin, 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.