Immunomodulatory role of bitter melon extract in inhibition of head and neck squamous cell carcinoma growth

Abstract

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer and leading cause of cancer related mortality worldwide. Despite the advancement in treatment procedures the overall survival rate of patients has not considerably enhanced in the past few decades. Therefore, new strategies to achieve a favorable response for the improvement in the prognosis of HNSCC are urgently needed. In this study, we examined the role of bitter melon extract (BME) in HNSCC tumor microenvironment. Mouse head and neck cancer (SCCVII) cells were subcutaneously injected into the flanks of syngeneic mice. We observed that oral gavage of BME significantly inhibits the tumor growth in mice as compared to control group. Further study suggested that BME inhibits cell proliferation as evident from low expression of proliferating cell nuclear antigen (PCNA) and c-Myc in the tumors of BME fed mice as compared to that of control group. We next investigated the role of BME as an immunomodulator in HNSCC model. Forkhead box protein P3⁺ (FoxP3⁺) T cells suppress tumor immunity. Our data suggested that BME treatment decreases the infiltrating regulatory T (Treg) cells by inhibiting FoxP3⁺ populations in the tumors and in spleens. Additionally, BME treatment reduces Th17 cell population in the tumor. However, BME treatment did not alter Th1 and Th2 cell populations. Together, our findings offer a new insight into how bitter melon extract inhibits head and neck tumor growth by modulating cell proliferation and Treg populations, with implications for how to control tumor-infiltrating lymphocytes and tumor progression.