Glycoborinine induces apoptosis through mitochondrial pathway in HepG2 cells

Glycoborinine (GB), a natural carbazole alkaloid isolated from Glycosmis pentaphylla, has been shown to be a potential molecule against Cancer cells. In this study, the cell-signaling pathway of its anti-tumor activity was investigated. MTT assay result showed that GB inhibited HepG2 cell proliferation in a dose- and time-dependent manner and 50% inhibiting concentration (IC50) of GB-induced cell death was 39.7 μM for a period of 48 h. GB-induced HepG2 Apoptosis was confirmed by Hochest 33258 staining and PI staining. The level of Reactive Oxygen Species (ROS) was measured with H2DCF-DA staining and the change of mitochondrial membrane potential (△Ψ(m)) was analyzed with tetrechloro-tetraethylbenzimidazolcarbocyanine iodide (JC-1) probe. Results showed that GB at 12.5, 25, and 50 μM promoted ROS production. GB induced HepG2 Apoptosis through a mitochondrial apoptotic pathway, which was demonstrated by GB-induced increase in the ratio of Bax/Bcl-2, cytochrome C release, the ratio of cleaved Caspase-3/procaspase-3, and the ratio of cleaved poly ADP-ribose polymerase (cleaved PARP)/poly ADP-ribose polymerase (PARP). To summarize, this study demonstrated that GB could induce HepG2 Apoptosis through the mitochondrial-dependent pathway, which might provide a promising approach to cure liver Cancer with GB.

anti-tumor activity; glycoborinine; mitochondrial apoptotic pathway.