FM807, a curcumin analogue, shows potent antitumor effects in nasopharyngeal carcinoma cells by heat shock protein 90 inhibition

// Min Ye 1, 3, * , Wei Huang 1, * , Wen-wei Wu 1 , Yang Liu 1 , Sheng-nan Ye 2 , Jian-hua Xu 1, 3 1 School of Pharmacy, Fujian Medical University, Fuzhou 350004, China 2 The First Affiliated Hospital of Fujian Medical University, Fuzhou 350004, China 3 Fuijan Provincial Key Laboratory of Natural Medicine Pharmacology, Fuzhou 350004, China * These authors contributed equally to this work Correspondence to: Sheng-nan Ye, email: yeshengnan63@yahoo.com Jian-hua Xu, email: xjh@mail.fjmu.edu.cn Keywords: FM807, nasopharyngeal carcinoma, epidermal growth factor receptor, β-catenin, Hsp90 inhibitor Received: August 17, 2016      Accepted: January 16, 2017      Published: February 01, 2017 ABSTRACT Nasopharyngeal carcinoma (NPC) is an epithelial malignancy usually associated with overexpression of both epidermal growth factor receptor (EGFR) and β-catenin. FM807 is a novel curcumin analogue with antitumor activity against both poorly and well-differentiated NPC cell lines as well as good selectivity for tumor cells. FM807 actions were shown to include inhibition of cell growth, induction of necrotic/late apoptotic cell death, and G1 arrest in NPC cells. Crucially, it exhibited potent antitumor effects both in vitro and in vivo . Binding of FM807 to the N-terminus of Hsp90 disrupted Hsp90/client complexes, resulting in degradation of the Hsp90 client protein EGFR and inhibition of the downstream Raf/MEK/ERK and PI3K/AKT pathway. FM807 also depleted levels of the intranuclear transcription factors β-catenin, Cyclin D1 and c-Myc levels by inhibiting Hsp90 chaperoned nuclear transport. In conjunction with its low toxicity in NPC xenograft mice, these results provide a sound preclinical basis for further development of FM807 as a novel therapeutic agent in the treatment of NPC.