Poster abstracts

Poster number 77 submitted by Courtney Nicholas

Apigenin induces apoptosis in leukemia, and inhibits inflammatory response in vitro and in vivo through an inhibition of NFkB-p65

Courtney Nicholas (pulmonary, allergy, and critical care; Graduate School), Melissa A Vargo (pulmonary, allergy, and critical care; Graduate School), Oliver H Voss (pulmonary, allergy, and critical care; Graduate School), Denis Guttridge (Comprehensive Cancer Center), Erich Grotewold (Plant cellular and molecular biology; Plant Biotechnology Center), Mark D Wewers (Internal Medicine; OSU Medical Center)

Abstract:
Macrophages are critical cells of the innate immune system, defending the organism against pathogens by initiating an inflammatory reaction. Recently, macrophages have also been implicated in tumor development and progression. Thus, the identification of anti-inflammatory molecules that specifically regulate macrophage behavior can be of great relevance in anti-cancer treatments. Apigenin is a plant polyphenol found in several fruits and vegetables. We previously found that apigenin induces apoptosis in leukemia. The objective of this study was to determine the potential anti-inflammatory effect of apigenin in human primary monocytes and in a mouse model of acute inflammation. To evaluate the effect of apigenin in apoptosis, THP-1 cells were treated with apigenin. Total proteins in treated cells were visualized and mass spectroscopy was performed to identify selected polypeptides. Release of inflammatory cytokines and NFkB transcriptional activity was examined in LPS-stimulated human primary monocytes and mouse macrophages. C57BL/6J mice were injected ip with apigenin prior to LPS challenge. We found that apigenin induced apoptosis in monocytic leukemia cells, stimulated the relocalization of histones into the cytoplasm, and inhibited the production of pro-inflammatory cytokines in LPS-stimulated human monocytes and mouse macrophages, even when administered post-challenge. We showed that apigenin inhibited the transcriptional activity of NF-kB in LPS-stimulated macrophages. Apigenin did not alter proteasomal degradation of IkBa, nor the NF-kB-DNA binding activity. However, apigenin suppressed the LPS-stimulated phosphorylation of NFkB-p65Ser536 by inhibiting the activation of IKKb kinase. Notably, apigenin reduced LPS-stimulated TNFa in a mouse model of acute inflammation. Moreover, apigenin completely suppressed the lethality induced by LPS in vivo. Apigenin had no significant effect on LPS-induced apoptosis in spleens. However, apigenin significantly decreased the percentage of infiltrated leukocytes in lungs of LPS-treated mice. These results show that apigenin is an anti-inflammatory agent in vitro and in vivo. Collectively, these findings elucidated a molecular mechanism and suggest a potential use of apigenin as an anti-inflammatory compound in acute inflammation.

Keywords: apigenin, cancer, inflammation