Xanthine oxidase inhibitory terpenoids of Amentotaxus formosana protect cisplatin-induced cell death by reducing reactive oxygen species (ROS) in normal human urothelial and bladder cancer cells
Journal
Phytochemistry
Journal Volume
71
Journal Issue
17-18
Pages
2140-2146
Date Issued
2010
Author(s)
Abstract
The diterpenoids (+)-ferruginol (1), ent-kaur-16-en-15-one (2), ent-8(14),15-sandaracopimaradiene-2α,18-diol (3), 8(14),15- sandaracopimaradiene-2α,18,19-triol (4), and (+)-sugiol (5) and the triterpenoids 3β-methoxycycloartan-24(241)-ene (6), 3β,23β-dimethoxycycloartan-24(241)-ene (7), 3β,23β-dimethoxy-5α-lanosta-24(241)-ene (8), and 23(S)-23-methoxy-24-methylenelanosta-8-en-3-one (9), isolated from Amentotaxus formosana, showed inhibitory effects on xanthine oxidase (XO). Of the compounds tested, compound 5 was a potent inhibitor of XO activity, with an IC 50 value of 6.8 ± 0.4 μM, while displaying weak ABTS radical cation scavenging activity. Treatment of the bladder cancer cell line, NTUB1, with 3-10 μM of compound 5 and 10 μM cisplatin, and immortalized normal human urothelial cell line, SV-HUC1, with 0.3-1 μM and 10-50 μM of compound 5 and 10 μM cisplatin, respectively, resulted in increased viability of cells compared with cytotoxicity induced by cisplatin. Treatment of NTUB1 with 20 μM cisplatin and 10 or 30 μM of compound 5 resulted in decreased ROS production compared with ROS production induced by cisplatin. These results indicate that 10 or 30 μM of compound 5 in NTUB1 cells may mediate through the suppression of XO activity and reduction of reactive oxygen species (ROS) induced by compound 5 cotreated with 20 μM cisplatin and protection of subsequent cell death. ? 2010 Elsevier Ltd. All rights reserved.
Subjects
Amentotaxaceae; Amentotaxus formosana; Antioxidant terpenoids; NTUB1; Reactive oxygen species; SV-HUC1
SDGs
Other Subjects
cisplatin; diterpene; reactive oxygen metabolite; sugiol; xanthine oxidase; article; cell death; chemistry; drug antagonism; drug effect; human; isolation and purification; stereoisomerism; Taxaceae; Cell Death; Cisplatin; Diterpenes; Humans; Reactive Oxygen Species; Stereoisomerism; Taxaceae; Xanthine Oxidase; Amentotaxus formosana
Type
journal article