title: Bitter melon reduces head and neck squamous cell carcinoma growth by targeting c-Met signaling.
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.
authors.affiliation: Department of Pathology, Saint Louis University, St. Louis, Missouri, United States of America.
authors.forename: Ananthi
authors.initials: A
authors.lastname: Rajamoorthi
authors.forename: Shubham
authors.initials: S
authors.lastname: Shrivastava
authors.forename: Robert
authors.initials: R
authors.lastname: Steele
authors.forename: Pratibha
authors.initials: P
authors.lastname: Nerurkar
authors.forename: Juan G
authors.initials: JG
authors.lastname: Gonzalez
authors.forename: Susan
authors.initials: S
authors.lastname: Crawford
authors.forename: Mark
authors.initials: M
authors.lastname: Varvares
authors.forename: Ratna B
authors.initials: RB
authors.lastname: Ray
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D019662:Cucurbitaceae / Q000737:chemistry*; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D010936:Plant Extracts / Q000627:therapeutic use; D019859:Proto-Oncogene Proteins c-met / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D000077195:Squamous Cell Carcinoma of Head and Neck; D023041:Xenograft Model Antitumor Assays
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D010936:Plant Extracts; C491743:MET protein, human; D019859:Proto-Oncogene Proteins c-met