title: Mechanisms of the anti-proliferative and anti-inflammatory effects of the herbal fixed combination STW 5 (Iberogast®) on colon adenocarcinoma (HT29) cells in vitro.
abstract: BACKGROUND
  Several conventional pharmaceuticals like non-steroidal anti-inflammatory drugs (NSAIDS) or selective cyclooxygenase-2 (COX-2) inhibitors have been demonstrated to exert anti-proliferative effects and to induce apoptosis in a variety of cell lines, e.g. colon, stomach, or prostate cancer cells. STW 5 (Iberogast(®)), a combination of nine plant extracts, is widely used in the treatment of gastrointestinal disorders, including functional dyspepsia and irritable bowel syndrome for which the involvement of an inflammatory etiology is discussed. To investigate the possible anti-proliferative effects, STW 5 and its components have been tested by using the colon-carcinoma cell line HT-29. The analyses have been performed in comparison to acetylsalicylic acid (ASA) and diclofenac (Diclo), which are well-known to reduce colon carcinoma risk.
  
  
  RESULTS
  STW 5 showed significant anti-proliferative and pro-apoptotic effects on HT-29 cancer cells, similar to NSAIDs under test. However, using the LDH assay, STW 5 revealed significantly lower cytotoxicity than Diclo at same concentrations. In contrast to NSAIDs, STW 5 induced COX-1/COX-2, caspase-3 and Bax mRNA expressions in HT-29 and blocked LPS mediated translocation of the NF-κB p65 from the cytoplasm into the nucleus in PMA-differentiated THP-1 macrophages. These effects might be relevant, e.g. for prevention of undesirable side effects like gastric erosions.
  
  
  CONCLUSIONS
  Our data suggest that the pro-apoptotic effect of STW 5 on HT-29 cells is involving multiple targets and is possibly due to an activation of the caspase cascade via mitochondrial destabilization. Active concentrations of STW 5 are, in relation to therapeutic doses, comparable to those of ASA and Diclo, suggesting a similar favorable effect on colon carcinoma risk.
authors.affiliation: Anatomy and Cell Biology, Department of Medical Cell Biology, University of Marburg, Robert-Koch-Str. 8, 35032 Marburg, Germany. gabriel.bonaterra@staff.uni-marburg.de
authors.forename: G A
authors.initials: GA
authors.lastname: Bonaterra
authors.forename: O
authors.initials: O
authors.lastname: Kelber
authors.forename: D
authors.initials: D
authors.lastname: Weiser
authors.forename: R
authors.initials: R
authors.lastname: Kinscherf
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001241:Aspirin / Q000494:pharmacology; D053148:Caspase 3 / Q000187:drug effects / Q000235:genetics; D002467:Cell Nucleus / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects*; D003106:Colon / Q000187:drug effects; D003110:Colonic Neoplasms / Q000188:drug therapy*; D051545:Cyclooxygenase 1 / Q000187:drug effects / Q000235:genetics; D051546:Cyclooxygenase 2 / Q000187:drug effects / Q000235:genetics; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D003593:Cytoplasm / Q000378:metabolism; D004008:Diclofenac / Q000494:pharmacology; D019073:HT29 Cells; D006801:Humans; D008264:Macrophages / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D010936:Plant Extracts / Q000494:pharmacology*; D021381:Protein Transport / Q000187:drug effects; D051028:bcl-2-Associated X Protein / Q000187:drug effects / Q000235:genetics
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D016861:Cyclooxygenase Inhibitors; D016328:NF-kappa B; D010936:Plant Extracts; D051028:bcl-2-Associated X Protein; C039964:iberogast; D004008:Diclofenac; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496511:PTGS1 protein, human; C496540:PTGS2 protein, human; D053148:Caspase 3; D001241:Aspirin