TriCurin, a novel formulation of curcumin, epicatechin gallate, and resveratrol, inhibits the tumorigenicity of human papillomavirus-positive head and neck squamous cell carcinoma

// Longzhu Piao 1, 2 , Sumit Mukherjee 3, 4 , Qing Chang 4, 5 , Xiujie Xie 1, 2 , Hong Li 6 , Mario R. Castellanos 7 , Probal Banerjee 3, 4 , Hassan Iqbal 1, 2 , Ryan Ivancic 1, 2 , Xueqian Wang 1, 2 , Theodoros N. Teknos 1, 2 and Quintin Pan 1, 2 1 Department of Otolaryngology-Head and Neck Surgery, The Ohio State University Medical Center, Columbus, Ohio, USA 2 Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, The Ohio State University Comprehensive Cancer Center, Columbus, Ohio, USA 3 Ph.D. Program in Biochemistry at the Graduate Center of the City University of New York, New York, USA 4 Department of Chemistry and Center for Developmental Neuroscience, College of Staten Island, Staten Island, New York, USA 5 Department of Pathology and Laboratory Medicine, Staten Island University Hospital, Northwell Health, Staten Island, New York, USA 6 Division of Pharmaceutics, College of Pharmacy, The Ohio State University, Columbus, Ohio, USA 7 Division of Research, Department of Medicine, Staten Island University Hospital, Northwell Health, Staten Island, New York, USA Correspondence to: Quintin Pan, email: Quintin.Pan@osumc.edu Keywords: human papillomavirus, p53, head and neck cancer, curcumin, catechin Received: December 22, 2015      Accepted: May 13, 2016      Published: July 16, 2016 ABSTRACT Head and neck squamous cell carcinoma (HNSCC) is the sixth most prevalent cancer worldwide with about 600,000 new cases diagnosed in the last year. The incidence of human papillomavirus-positive head and neck squamous cell carcinoma (HPV-positive HNSCC) has rapidly increased over the past 30 years prompting the suggestion that an epidemic may be on the horizon. Therefore, there is a clinical need to develop alternate therapeutic strategies to manage the growing number of HPV-positive HNSCC patients. TriCurin is a composition of three food-derived polyphenols in unique stoichiometric proportions consisting of curcumin from the spice turmeric, resveratrol from red grapes, and epicatechin gallate from green tea. Cell viability, clonogenic survival, and tumorsphere formation were inhibited and significant apoptosis was induced by TriCurin in UMSCC47 and UPCI:SCC090 HPV-positive HNSCC cells. Moreover, TriCurin decreased HPV16E6 and HPV16E7 and increased p53 levels. In a pre-clinical animal model of HPV-positive HNSCC, intra-tumoral injection of TriCurin significantly inhibited tumor growth by 85.5% compared to vehicle group ( P < 0.05, n = 7). Our results demonstrate that TriCurin is a potent anti-tumor agent for HPV-positive HNSCC. Further development of TriCurin as a novel anti-cancer therapeutic to manage the HPV-positive HNSCC population is warranted.