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Chelidonine and Homochelidonine Induce Cell Death through Cell Cycle Checkpoints and MAP Kinase Pathways

Publication at Faculty of Medicine in Hradec Králové |
2017

Abstract

This study focuses on the comparative in vitro cytotoxicity of chelidonine and homochelidonine on human cancer and non-cancer cells. Both alkaloids produced a decrease in cellular growth in a dose-dependent manner exhibiting greater potency in cancer cells.

The growth inhibitory effect was evidenced in both ovarian carcinoma A2780 and lung fibroblast MRC-5 cells by inducing G2 and mitotic phase cell cycle arrest. Results indicated that the extent of apoptosis induced by chelidonine and homochelidonine was correlated to sensitivity to the antiproliferative activity of the evaluated compounds.

Western blotting suggested that the cellular toxicological mechanism of chelidonine is related to the differential upregulation of phospho-Chk2, p21(Cip1/Waf1), phospho-ERK1/2 and phospho-p38 in various cell types, leading to alternations in the suppression of proliferation and either induction or prevention of apoptosis. Chelidonine showed the more potent effects and also affected the cell cycle checkpoints and MAPK signaling pathways within cells.