LAUSR

Oral squamous cell carcinoma (OSCC) is a complex malignancy and tobacco habit is one of the main etiological factors. Our previous study showed potential chemopreventive effect of bitter melon (Momordica charantia) extract (BME) in different pre-clinical cancer models like head and neck, breast, prostate. The aim of this study is to understand the molecular mechanism of BME in prevention of carcinogen induced in-vivo oral carcinogenesis. For this purpose, we induced oral cancer in immunocompetent mice by using tobacco associated carcinogen 4-nitroquinoline 1-oxide (4-NQO), and treated with BME through their drinking water. We observed that BME feeding significantly reduced the incidence of 4-NQO induced oral cancer. Histological analysis showed moderate dysplasia to invasive squamous cell carcinoma in 4NQO treated mice tongue, whereas no remarkable changes were seen in the BME-fed mice. RNA-seq data showed differential expression of several genes during carcinogenesis and during prevention of the cancer. We previously showed that BME treatment decreases the infiltrating regulatory T (Treg) cells by inhibiting FoxP3+ populations in the tumors and in spleens, suggesting an immunomodulatory role of BME in prevention. Here, we observed elevated expression of pro-inflammatory genes s100a9, IL23a, IL-1β and immune check point gene PDCD1/PD1 of the pathway, during oral cancer development. Interestingly, BME treatment significantly reduced the expression of these molecules. Subsequently, we observed the enhancement of MMP9 during carcinogenesis, which was reduced in BME-fed mouse tongue tissues. Taken together, our observation strongly demonstrated a chemopreventive effect of BME on carcinogen induced oral cancer. Citation Format: Subhayan Sur, Robert Steele, Ratna B. Ray. Bitter melon extract modulates immune signaling in prevention of tobacco associated carcinogen induced oral carcinogenesis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5203.