Nonapoptotic cell death induced by Hypericum species on cancer cells

Objective. There are approximately 400 Hypericum species that grow naturally in different geographic origins of the world. Those species have been used in different folk medicines and screened for their biological activity including cancer. Our country is an important place for Hypericum species which are known as “kantaron, binbirdelik otu, kan otu, kılıç otu, yaraotu, kuzukıran”. We therefore evaluated the possible cytotoxic/apoptotic activities, total phenolic content and antioxidant capacity of the crude methanol extracts Hypericum adenotrichum Spach. and Hypericum olympicum L. which are still used in Turkish folk medicine. Methods. The total phenolic content and antioxidant capacity were determined by Folin-Ciocalteu and ABTS methods. Anti-growth effects were screened in human hepatoma (Hep3B) and rat glioma (C6) cell lines by the MTT and ATP viability assays. The cell death mode (apoptosis/necrosis) was investigated by fluorescence imaging and the level of caspase-cleaved cytokeratin 18 (M30), active caspase-3 and cleaved PARP (poly (ADP-ribose) polymerase). Results. The results indicate that the crude methanol extracts of Hypericum olympicum L. and Hypericum adenotrichum have both anti-growth/cytotoxic activities on these cells in a dose dependent manner. Conclusion. These extracts clearly induced non-apoptotic cell death in human hepatoma (Hep3B) and rat glioma (C6) cell lines.