In vitro and in vivo investigations on the antitumour activity of Chelidonium majus

Background Chelidonium majus L. (Papaveraceae) (greater celandine) is a medicinal herb that is widely spread in Europe. Antitumoural activity has been reported for C. majus extracts. Hypothesis/Purpose To investigate the antitumour activity of a C. majus extract in vitro and in vivo. Study Design Cytotoxic effects of C. majus extracts were evaluated on human cancer cell lines, i.e. PANC-1 (pancreas cancer), HT-29 (colon cancer), MDA-MB-231 (breast cancer), PC-EM005 and PC-EM002 (primary endometrium cancer cells), and PANC02 (murine pancreatic adenocarcinoma cells). A preliminary in vivo study was performed to evaluate the effect of a defatted C. majus extract and Ukrain^TM in a highly metastatic murine pancreatic model. Methods Chelidonium majus L. herb containing 1.26% (dry weight) of total alkaloids expressed as chelidonine was used to prepare an 80% ethanolic extract (CM2). This crude extract was then defatted with n-hexane, resulting in a defatted C. majus extract (CM2B). Cytotoxic effects of the two extracts (CM2 and CM2B) were evaluated on human and murine cell lines in vitro. CM2B and Ukrain^TM were evaluated in a highly metastatic murine pancreatic model. Results Four main benzylisoquinoline alkaloids were identified in CM2B, i.e. chelidonine, sanguinarine, chelerythrine and protopine, using HPLC-UV. CM2 showed a high cytotoxic activity against PANC-1 (IC₅₀, 20.7 μg/ml) and HT-29 (IC₅₀, 20.6 μg/ml), and a moderate cytotoxic activity against MDA-MB-231 (IC₅₀, 73.9 μg/ml). CM2 as well as CM2B showed a moderate to high cytotoxic activity against the PANC02 cell line (IC₅₀, 34.4 and 36.0 μg/ml). Low to almost no cytotoxic effect was observed on primary endometrium cancer cells PC-EM005, PC-EM002 and on normal fibroblast cells 3T3, when treated with CM2B. Significantly less metastases were counted in mice treated with 1.2 mg/kg CM2B, but not with 3.6 mg/kg Ukrain^TM, compared to the control group. The extract, however, did not affect the weight of the primary tumours.