Effect of 2alpha-hydroxyursolic acid on NF-kappaB activation induced by TNF-alpha in human breast cancer MCF-7 cells.
Apples are one of the largest contributors of fruit phenolics of all fruits consumed by Americans and contain a variety of bioactive compounds, which have health benefits. Consumption of apples has been linked to reduced risk of chronic diseases such as cancer and cardiovascular disease. Apple extracts have been shown to have the capabilities of inhibiting NF-kappaB activation in human breast cancer MCF-7 cells. 2Alpha-hydroxyursolic acid is one of the major triterpenoids isolated from apple peels, and its effects on cell proliferation and TNF-alpha-induced NF-kappaB activation in MCF-7 cells were examined. 2Alpha-hydroxyursolic acid significantly inhibited MCF-7 cell proliferation at doses of 20 microM (p < 0.05). Preincubation with 2alpha-hydroxyursolic acid suppressed TNF-alpha-induced NF-kappaB activation in a dose-dependent manner and significantly inhibited the activation at a dose of 20 microM of 2alpha-hydroxyursolic acid (p < 0.05). 2Alpha-hydroxyursolic acid treatment did not affect the phosphorylation level of NF-kappaB inhibitor (IkappaB-alpha), but proteasome activity in MCF-7 cells was inhibited significantly at doses of 10 and 20 microM ( p < 0.05). These results suggest that 2alpha-hydroxyursolic acid has antiproliferative activities against MCF-7 cells and capabilities inhibiting NF-kappaB activation induced by TNF-alpha partially by suppressing proteasome activities.
Yoon
Hyungeun
H
Department of Food Science, Cornell University, Ithaca, New York 14853-7201, USA.
Liu
Rui Hai
RH
D016588:Anticarcinogenic Agents / Q000494:pharmacology; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D005638:Fruit / Q000737:chemistry*; D006801:Humans; D027845:Malus / Q000737:chemistry*; D016328:NF-kappa B / Q000187:drug effects*; D014315:Triterpenes / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
C412810:2-hydroxyursolic acid; D016588:Anticarcinogenic Agents; D016328:NF-kappa B; D014315:Triterpenes; D014409:Tumor Necrosis Factor-alpha