Mechanistic Insights of BME mediated inhibition of head and neck cancer growth

Saint Louis University, Saint Louis MO

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Abstract

? DESCRIPTION (provided by applicant): Head and neck squamous cell carcinoma (HNSCC) refers to a group of biologically similar cancers that start in the lip, tongue, oral cavity (mouth, nasal cavity (inside the nose), paranasal sinuses, pharynx, and larynx. HNSCC is the sixth most common cancer worldwide, and accounts for about 3-5% of all cancers in the United States. American Cancer society estimates 55,070 people will develop head and neck cancers in 2014. The 5- year survival rate of HNSCC patients is ~60% and has improved only marginally during the past few decades. Although improvements in surgical techniques, chemotherapy and radiation delivery, and supportive care have improved quality of life for patients with HNSCC, the regional and distant recurrence remain common and is almost always fatal. The impact of current cytotoxic therapies for HNSCC is limited by disease recurrence and resistance to therapy. Thus, there is a tremendous need for development of targeted and effective therapies. We have recently identified a plant-derived natural product, bitter melon extract (BME), which can induce HNSCC cell death. We have observed that BME treatment on HNSCC cells inhibits c-Met/EGFR and downstream signaling molecules (Stat3, c-myc and Mcl-1), and enhances natural killer (NK) cell activity, implicating its potential role in inhibition of head and neck cacer. The long-term objective of our project is to evaluate preventive and therapeutic efficacy of BME against HNSCC and understanding the underlying mechanisms. We hypothesize that BME and its active component(s) will prevent and inhibit HNSCC by multiple mechanisms including: modulation of genes critical to cancer progression, effect on cancer stem-like cells and tumor microenvironment in preclinical animal models. Results from this study will extend and translate our findings to future clinical studies. Innovation: Our application will examine for the first tim the mechanistic, preventive, and therapeutic effect of BME in highly relevant HNSCC animal models.