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

Capistrano I., Rica, Wouters, An, Lardon, Filip, Gravekamp, Claudia, Apers, Sandra, Pieters, Luc
Phytomedicine 2015 v.22 pp. 1279-1287
Chelidonium majus, adenocarcinoma, antineoplastic activity, breast neoplasms, colorectal neoplasms, cytotoxicity, endometrium, fibroblasts, hexane, high performance liquid chromatography, humans, in vivo studies, inhibitory concentration 50, medicinal plants, metastasis, mice, neoplasm cells, pancreatic neoplasms, sanguinarine, Europe
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.To investigate the antitumour activity of a C. majus extract in vitro and in vivo.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 UkrainTM in a highly metastatic murine pancreatic model.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 UkrainTM were evaluated in a highly metastatic murine pancreatic model.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 UkrainTM, compared to the control group. The extract, however, did not affect the weight of the primary tumours.