Abstract 703: Suppression of neurotensin receptor type 1 expression and function by apigenin in human colorectal cancers involves protein kinase CK2/JNK pathway

Abstract

Abstract Apigenin, a nonmutagenic chemopreventive agent found naturally in fruits and green vegetables, is an inhibitor of protein kinase CK2 (formerly casein kinase II), which is frequently upregulated in human cancers. Neurotensin (NT), a gut peptide, stimulates growth of colorectal cancers (CRCs) through its high affinity receptor (NTR1). In this study, we found that treatment with apigenin suppressed NTR1 expression in CRC cells HCT116, SW480 and SW620. Additionally, treatment with emodin, another natural inhibitor of CK2, and TBB (4,5,6,7-tetrabromo-1H-benzotriazole), a selective chemical inhibitor of CK2, suppressed NTR1 expression in these CRC cells, indicating that CK2 plays a role in NTR1 regulation. Moreover, apigenin significantly decreased phosphorylation of JNK1/2, whereas TBB decreased phosphorylation of JNK1 and emodin decreased phosphorylation of JNK2 in HCT116 cells; all three compounds decreased phosphorylation of JNK1 in SW480 cells. Treatment with the selective JNK1/2 inhibitor, SP600125, suppressed NTR1 expression in all CRC cell lines examined. Furthermore, apigenin significantly inhibited CRC cell proliferation and prevented NT-stimulated expression of IL-8, c-myc and Mcl-1, all which contribute to CRC proliferation or metastasis. We conclude that apigenin suppresses endogenous NTR1 expression and function in multiple CRC cell lines; this effect may involve CK2/JNK signaling. The downregulation of NTR1 in CRCs may represent an important mechanism for the anti-cancer effects of apigenin. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 703.