Terpenoids induce cell cycle arrest and apoptosis from the stems of Celastrus kusanoi associated with reactive oxygen species.
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.
Chen
Hui-Ling
HL
Faculty of Pharmacy, College of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan.
Lin
Kai-Wei
KW
Huang
A-Mei
AM
Tu
Huang-Yao
HY
Wei
Bai-Luh
BL
Hour
Tzyh-Chyuan
TC
Yen
Ming-Hong
MH
Pu
Yeong-Shiou
YS
Lin
Chun-Nan
CN
D017209:Apoptosis / Q000187:drug effects*; D031247:Celastrus / Q000737:chemistry*; D002453:Cell Cycle / Q000187:drug effects*; D045744:Cell Line, Tumor; D006801:Humans; D010936:Plant Extracts / Q000494:pharmacology*; D018547:Plant Stems / Q000737:chemistry; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013729:Terpenes / Q000494:pharmacology*; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology
D010936:Plant Extracts; D017382:Reactive Oxygen Species; D013729:Terpenes