Research Papers:
FM807, a curcumin analogue, shows potent antitumor effects in nasopharyngeal carcinoma cells by heat shock protein 90 inhibition
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Abstract
Min Ye1,3,*, Wei Huang1,*, Wen-wei Wu1, Yang Liu1, Sheng-nan Ye2, Jian-hua Xu1,3
1School of Pharmacy, Fujian Medical University, Fuzhou 350004, China
2The First Affiliated Hospital of Fujian Medical University, Fuzhou 350004, China
3Fuijan Provincial Key Laboratory of Natural Medicine Pharmacology, Fuzhou 350004, China
*These authors contributed equally to this work
Correspondence to:
Sheng-nan Ye, email: [email protected]
Jian-hua Xu, email: [email protected]
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.
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PII: 14970