Phloroglucinols inhibit chemical mediators and xanthine oxidase, and protect cisplatin-induced cell death by reducing reactive oxygen species in normal human urothelial and bladder cancer cells.
Phloroglucinols, garcinielliptones HA-HE (1-5), and C (6) were studied in vitro for their inhibitory effects on chemical mediators released from mast cells, neutrophils, and macrophages. Compound 6 revealed significant inhibitory effect on release of lysozyme from rat neutrophils stimulated with formyl-Met-Leu-Phe (fMLP)/cytochalasin B (CB). Compounds 3, 4, and 6 showed significant inhibitory effects on superoxide anion generation in rat neutrophils stimulated with (fMLP)/(CB), while compounds 1 and 5 revealed inhibitory effects on tumor necrosis factor-alpha (TNF-alpha) formation in macrophages stimulated with lipopolysaccharide (LPS). Compounds 1 and 3-6 showed inhibitory effects on xanthine oxidase (XO) and could inhibit the DNA breakage caused by O2(-*). Treatment of NTUB1 with 2 to 60 microM compound 3 and 5 microM cisplatin and SV-HUC1 with 9 to 60 microM 3 and 5 microM cisplatin, respectively, resulted in an increase of viability of cells. These results indicated that compounds 1 and 3-6 showed anti-inflammatory effects and antioxidant activities. Compound 3 mediates through the suppression of XO activity and reduction of reactive oxygen species (ROS), and protection of subsequent cell death.
Lin
Kai-Wei
KW
School of Pharmacy, Kaohsiung Medical University, Kaohsiung 807, Taiwan.
Huang
A-Mei
AM
Tu
Huang-Yao
HY
Weng
Jing-Ru
JR
Hour
Tzyh-Chyuan
TC
Wei
Bai-Luh
BL
Yang
Shyh-Chyun
SC
Wang
Jih-Pyang
JP
Pu
Yeong-Shiau
YS
Lin
Chun-Nan
CN
D000818:Animals; D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D016923:Cell Death / Q000187:drug effects*; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D029760:Garcinia / Q000737:chemistry; D006801:Humans; D008264:Macrophages / Q000187:drug effects / Q000276:immunology; D008407:Mast Cells / Q000187:drug effects; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology; D010696:Phloroglucinol / Q000494:pharmacology*; D051381:Rats; D017382:Reactive Oxygen Species / Q000032:analysis / Q000037:antagonists & inhibitors; D014315:Triterpenes / Q000494:pharmacology; D001749:Urinary Bladder Neoplasms / Q000737:chemistry* / Q000201:enzymology / Q000473:pathology; D019459:Urothelium / Q000737:chemistry; D014969:Xanthine Oxidase / Q000037:antagonists & inhibitors*
D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D004791:Enzyme Inhibitors; D017382:Reactive Oxygen Species; D014315:Triterpenes; C114803:garcinielliptone; D010696:Phloroglucinol; D014969:Xanthine Oxidase; D002945:Cisplatin