Mechanisms of the anti-proliferative and pro-apoptotic effect of the herbal fixed combination STW 5 on colon adenocarcinoma cells in vitro

The herbal preparation STW 5 is widely used in the treatment of functional dyspepsia and other motility-related gastrointestinal disorders. Our objective was to determine the molecular mechanisms of the anti-proliferative and pro-apoptotic effects on colon adenocarcinoma cells (HT-29). Cells were treated with diclofenac (Diclo), aspirin (ASA), STW 5 or its components STW 6 (Iberis amara totalis), STW 5-K II (peppermint), STW 5-K VII (milk thistle) or STW 5-K VIII (lemon balm). Anti-proliferative effects were measured with sulforhodamine. Apoptosis was identified by YO-PRO-1® staining. Treatment with Diclo (0.1 mM), ASA (2.5 mM), STW 5 (100µ g/ml) or its components STW 6 (12.5µ g/ml), STW 5-K II (50µ g/ml), STW K VII (100µ g/ml) or STW 5-K VIII (25µ g/ml) inhibited proliferation by ca. 50–60% (ASA or Diclofenac 45–50%). STW 5 (as well as ASA or Diclo) induced apoptosis 3 to 4- fold. 100µg/ml STW 5 showed a 20% or 30% induction of Caspase-3 or BAX expression, whereas ASA or Diclo revealed inhibitory effects. 100µg/ml STW 5 inhibited the Bcl2 mRNA expression. STW 25–100µg/ml up-regulated the expression of NFkB p65 subunit. Our data suggest that STW 5 and some of its components show antiproliferative and pro-apoptotic effects on HT-29 cells in vitro, possibly due to an activation of the caspase cascade and the NFkB pathway. Active concentrations of STW 5 are, in relation to therapeutic doses, comparable to those of ASA and Diclo, suggesting a similar favourable effect on colon carcinoma risk.