Terpenoids induce cell cycle arrest and apoptosis from the stems of Celastrus kusanoi associated with reactive oxygen species.
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Abstract
Bioguided fractionation of the CHCl(3) extracts obtained from Celastrus kusanoi stems led to isolation of two new terpenoids, 3beta-hydroxy-11,14-oxo-abieta-8,12-diene (1) and 3beta-trans-(3,4-dihydroxycinnamoyloxy)-11alpha-methoxy-12-ursene (2), and four known compounds characterized by spectroscopic methods. Compounds 1 and 2 and known triterpenoid erythrodiol (3) exhibited cytotoxic activity against bladder cancer cells (NTUB1) with IC(50) values of 58.2 +/- 2.3, 160.1 +/- 60.9, and 18.3 +/- 0.5 microM, respectively. Exposure of NTUB1 to 3 (5 and 10 microM) for 24 h significantly increased the level of production of reactive oxygen species (ROS). Flow cytometric analysis showed that treatment of NTUB1 with 3 led to the cell cycle arrest at G0/G1 accompanied by an increase in the extent of apoptotic cell death after 24 h. These data suggest that the presentation of G1 phase arrest and apoptosis in 3-treated NTUB1 for 24 h was mediated through an increased amount of ROS in cells exposed to 3.