Coadministration of a Gloriosa superba extract improves the in vivo antitumoural activity of gemcitabine in a murine pancreatic tumour model

Background: Gloriosa superba L. (glory lily, Colchicaceae) contains colchicine, and related alkaloids such as 3-0-demethylcolchicine and its glycoside colchicoside. Previously the in vivo efficacy of a crude extract and a colchicine-poor I colchicoside-rich extract of G. superba seeds was shown in a murine model of pancreatic adenocarcinoma. Hypothesis/Purpose: The efficacy can be improved without obvious signs of toxicity by increasing the treatment dose; the efficacy of gemcitabine can be improved by coadministration of a Gloriosa superba extract. Study design: A survival experiment was carried out in a murine model of pancreatic adenocarcinoma and the semi-long-term toxicity of both G. superba extracts was determined; a combination therapy with gemcitabine was evaluated. Methods: A crude ethanolic extract (GS) and a colchicine-poor colchicoside-rich extract (GS2B) were prepared, containing 3.22% colchicine, 2.52% colchicoside and 1.52% 3-0-demethylcolchicine (GS), and 0.07%, 2.26% and 0.46% (m/m) (GS2B). They were evaluated in a murine model of pancreatic adenocarcinoma at a dose of 4.5 mg/kg (p.o., daily) total content of colchicine and derivatives during 3 weeks, or at 3.0 mg/kg (p.o., daily) combined with gemcitabine (60 mg/kg, i.p., 3x/week) during 54 days. Results: A significant effect in tumour growth over time was observed for gemcitabine and the combination therapy compared to the control group. No significant difference was observed for the groups treated with colchicine and both extracts. However, combination therapy was significantly better than the monotherapy with gemcitabine. Moreover, survival analysis showed a significant prolongation of the survival of the groups treated with gemcitabine and the combination therapy. A slight difference in survival was observed between gemcitabine and the combination therapy, the latter one being slightly better. No significant prolongation of survival was observed for the extracts and colchicine compared to the control group. Conclusion: Although a relevant tumour growth inhibition and a difference of relative tumour volume compared to the control group were observed on day 11, and a slightly longer survival was noticed for GS2B, the most important conclusion from this study is that the crude G. superba extract (GS) might have an added value combined with gemcitabine in the treatment of pancreatic tumours. (C) 2016 Elsevier GmbH. All rights reserved.