Effect of selected phytochemicals and apple extracts on NF-kappaB activation in human breast cancer MCF-7 cells.
Nuclear factor kappaB (NF-kappaB) is a transcription factor, which plays an important role in inflammation, cell proliferation, apoptosis, and immunity in eukaryotes. In cancer cells, NF-kappaB induces resistance to anticancer chemotherapeutic agents by increasing cell proliferation and inhibiting apoptosis. Therefore, inhibition of NF-kappaB activation in cancer cells is advantageous in cancer therapy by lowing the resistance to chemotherapy. Several phytochemicals from fruits and vegetables have been reported to inhibit NF-kappaB activation, but the mechanisms of how the phytochemicals work have not been fully understood. The present study examines the effects of selected phytochemicals and apple extracts on TNF-alpha-induced NF-kappaB activation in human breast cancer MCF-7 cells. Apple extracts significantly inhibited the TNF-alpha-induced NF-kappaB activation at a dose of 5 mg/mL (p < 0.05). Curcumin also significantly blocked the TNF-alpha-induced NF-kappaB activation at doses of 10 and 20 microM (p < 0.05). Neither apple extracts nor curcumin affected phosphorylation of inhibitor of NF-kappaB-alpha (IkappaB-alpha); both significantly inhibited proteasomal activity of MCF-7 cells at doses of 2.5 and 5 mg/mL of apple extracts and 20 microM of curcumin (p < 0.05). These results suggest that apple extracts and curcumin have the capabilities of inhibiting TNF-alpha-induced NF-kappaB activation of MCF-7 cells by inhibiting the proteasomal activities instead of IkappaB kinase (IKK) activation.
Yoon
Hyungeun
H
Department of Food Science and Institute of Comparative and Environmental Toxicology, 108 Stocking Hall, Cornell University, Ithaca, New York 14853-7201, USA.
Liu
Rui Hai
RH
D001943:Breast Neoplasms / Q000378:metabolism*; D045744:Cell Line, Tumor; D005638:Fruit / Q000737:chemistry*; D006801:Humans; D027845:Malus / Q000737:chemistry*; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000187:drug effects / Q000502:physiology; D010936:Plant Extracts / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D016328:NF-kappa B; D010936:Plant Extracts; D014409:Tumor Necrosis Factor-alpha