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

The diterpenoids (+)-ferruginol (1) ent-kaur-16-en-15-one (2) ent-8(14) 15-sandaracopimaradiene-2 alpha 18-diol(3) 8(14) 15-sandaracopimaradiene-2 alpha 18 19-triol (4) and (+)-sugiol (5) and the triterpenoids 3 beta-methoxycycloartan-24(24(1))-ene (6) 3 beta 23 beta-dimethoxycycloartan-24(24(1))-ene (7) 3 beta 23 beta-dimethoxy-5 alpha-lanosta-24(24(1))-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 IC50 value of 68 +/- 04 mu M while displaying weak ABTS radical cation scavenging activity Treatment of the bladder cancer cell line NTUB1 with 3-10 mu M of compound 5 and 10 mu M cisplatin and immortalized normal human urothelial cell line SV-HUC1 with 03-1 mu M and 10-50 mu M of compound 5 and 10 mu M cisplatin respectively resulted in increased viability of cells compared with cytotoxicity induced by cisplatin Treatment of NTUB1 with 20 mu M cisplatin and 10 or 30 mu M of compound 5 resulted in decreased ROS production compared with ROS production induced by cisplatin These results indicate that 10 or 30 mu M 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 mu M cisplatin and protection of subsequent cell death (C) 2010 Elsevier Ltd All rights reserved