Xanthine oxidase inhibitory triterpenoid and phloroglucinol from guttiferaceous plants inhibit growth and induced apoptosis in human NTUB1 cells through a ROS-dependent mechanism.

A known triterpenoid, β-amyrin (1), and a known and a new phloroglucinol, cohulupone (2) and garcinielliptone P (3), were isolated from the pericarp and heartwood and seed of Garcinia subelliptica, respectively. A new xanthonolignoid, hyperielliptone HF (4), was isolated from the heartwood of Hypericum geminiflorum. The new compounds were established by analysis of their spectroscopic data. Compounds 1-3 showed an inhibitory effect on xanthine oxidase (XO). Treatment of NTUB1, a human bladder cancer cell, with 1 or 1 cotreated with cisplatin for 24 h resulted in a decreased viability of cells. Exposure of NTUB1 to 1 or 1 cotreated with cisplatin for 24 h significantly increased the level of production of reactive oxygen species (ROS). Flow cytometric analysis indicated that treatment of NTUB1 with 1 or 1 cotreated with cisplatin led to the cell cycle arrest, accompanied by an increase in the extent of apoptotic cell death in 1 or 1 combined with cisplatin-treated NTUB1 after 24 h. These data suggested that the presentation of cell cycle arrest and apoptosis in 1 or 1 combined with cisplatin-treated NTUB1 for 24 h was mediated through an increased amount of ROS in cells exposed to 1 or 1 cotreated with cisplatin.