Bitter Melon Reduces Head and Neck Squamous Cell Carcinoma Growth by Targeting c-Met Signaling |
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| Authors: | Ananthi Rajamoorthi Shubham Shrivastava Robert Steele Pratibha Nerurkar Juan G. Gonzalez Susan Crawford Mark Varvares Ratna B. Ray |
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| Affiliation: | 1. Department of Pathology, Saint Louis University, St. Louis, Missouri, United States of America.; 2. Saint Louis University Cancer Center, Saint Louis University, St. Louis, Missouri, United States of America.; 3. Laboratory of Metabolic Disorders and Alternative Medicine, Department of Molecular Biosciences and Bioengineering, College of Tropical Agriculture and Human Resources, University of Hawaii, Honolulu, Hawaii, United States of America.; Ohio State University, United States of America, |
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| Abstract: | Head and neck squamous cell carcinoma (HNSCC) remains difficult to treat, and despite of advances in treatment, the overall survival rate has only modestly improved over the past several years. Thus, there is an urgent need for additional therapeutic modalities. We hypothesized that treatment of HNSCC cells with a dietary product such as bitter melon extract (BME) modulates multiple signaling pathways and regresses HNSCC tumor growth in a preclinical model. We observed a reduced cell proliferation in HNSCC cell lines. The mechanistic studies reveal that treatment of BME in HNSCC cells inhibited c-Met signaling pathway. We also observed that BME treatment in HNSCC reduced phosphoStat3, c-myc and Mcl-1 expression, downstream signaling molecules of c-Met. Furthermore, BME treatment in HNSCC cells modulated the expression of key cell cycle progression molecules leading to halted cell growth. Finally, BME feeding in mice bearing HNSCC xenograft tumor resulted in an inhibition of tumor growth and c-Met expression. Together, our results suggested that BME treatment in HNSCC cells modulates multiple signaling pathways and may have therapeutic potential for treating HNSCC. |
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