Chelidonine Induces Caspase-Dependent and Caspase-Independent Cell Death through G(2/M) Arrest in the T98G Human Glioblastoma Cell Line

Abstract

Chelidonium majus L. (family Papaveraceae), commonly known as greater celandine or tetterwort, has been reported to have antibacterial and anticancer effects and chelidonine is known as a functional metabolite extracted from C. majus. In this study, we observed the cytotoxicity of the alkaloid, chelidonine, and investigated its functional mechanism in T98G glioblastoma cell line. Chelidonine induced apoptosis in a dose-dependent manner, which was accompanied by decreased antiapoptotic protein Mcl-1. Caspase-3 and -9 were activated by treatment with chelidonine, but chelidonine-mediated apoptosis was only partially inhibited by a pan-caspase inhibitor. Chelidonine also induced the translocation of AIF into the nucleus; therefore, it is likely that chelidonine induces T98G cell death through both caspase-dependent and caspase-independent apoptosis pathways. Chelidonine also induced G2/M arrest by inducing multipolar spindle assembly, which might also lead to cell death through inhibiting mitosis. Active CDK1, one of factors contributing to the prolongation of G2/M phase, induced Mcl-1 degradation increasing mitochondrial instability, which is also an inducer of apoptosis in chelidonine-treated T98G cells. Taken together, these findings indicate that chelidonine induces apoptosis through G2/M arrest and Mcl-1 degradation, implying that it may represent a compound for anticancer chemotherapy.