1. Cafestol, a coffee diterpene, inhibits urotensin II-induced interleukin-8 expression in human umbilical vein endothelial cells
- Author
-
Wen Ray Haw, Shih-Hurng Loh, Ju Chi Liu, Tzu Hurng Cheng, Po-Yuan Chen, Chien Sung Tsai, Shu Fu Huang, Yi-Ting Tsai, Li Chin Sung, and Chun Chao Chen
- Subjects
0301 basic medicine ,Angiogenesis ,Urotensins ,Cafestol ,Intracellular Space ,Umbilical vein ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,medicine ,Human Umbilical Vein Endothelial Cells ,Humans ,Interleukin 8 ,Pharmacology ,Dose-Response Relationship, Drug ,Cell growth ,Interleukin-8 ,Cell biology ,Endothelial stem cell ,030104 developmental biology ,chemistry ,Gene Expression Regulation ,030220 oncology & carcinogenesis ,Signal transduction ,Diterpenes ,Urotensin-II ,medicine.drug - Abstract
Cafestol, a diterpene molecule found in the berries of Coffea arabica L. (Rubiaceae), has been shown to exercise anti-angiogenic and anti-tumorigenic effects. However, cafestol's cellular mechanism has yet to be fully investigated. We previously demonstrated that urotensin II enhanced interleukin-8 secretion by endothelial cells, thereby increasing endothelial cell proliferation. Urotensin II may also participate in angiogenesis and tumor infiltration by macrophages. However, the effects of cafestol on urotensin II-induced interleukin-8 expression and cellular proliferation have not been determined. Here, we showed that pretreatment with cafestol inhibited urotensin II-stimulated endothelial cell proliferation. Further experiments demonstrated that cafestol increased translocation of nuclear factor erythroid 2-related factor 2 (Nrf2) and expression of enhanced heme oxygenase-1. Moreover, cafestol inhibited expression of urotensin II-induced interleukin-8. Cafestol's inhibitory effects on interleukin-8 expression and cellular proliferation induced by urotensin II were significantly abrogated by heme oxygenase-1 silencing, suggesting it may be involved in mediating the effects of cafestol. This study reports that cafestol inhibits urotensin II-induced interleukin-8 expression and cell proliferation via Nrf2/heme oxygenase-1-dependent mechanism in endothelial cells. These findings provide novel insight into the signaling pathways that may be important in mediating the effects of cafestol.
- Published
- 2017