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.

Indomethacin and juglone inhibit inflammatory molecules to induce apoptosis in colon cancer cells

“…[9,10] Regular intake of indomethacin may, however, result in side effects, especially, gastric ulceration [11] by decreasing blood flow into the mucosal regions and increasing gastric juice volume, leading to decrease in gastric pH. [14][15][16] Recently, compounds isolated from natural products were found to be beneficial in treating various metabolic diseases, including cancer. [14][15][16] Recently, compounds isolated from natural products were found to be beneficial in treating various metabolic diseases, including cancer.…”

Bitter Melon Enhances Natural Killer–Mediated Toxicity against Head and Neck Cancer Cells

“…In addition to its direct inhibitory effect on tumor growth and survival, BME also has demonstrated immunomodulatory activity in a syngeneic mouse model of HNSCC by inhibiting Treg activity (14). However, the effect of BME on NK cell activation and subsequently killing of HNSCC cells was unknown.…”

“…Based on our in vitro data, we examined granzyme B and CD107a/LAMP1 expression in tumor tissues from HNSCC syngeneic mouse (14). We performed Western blot analysis and qRT-PCR to examine the status of granzyme B in tumor following BME treatment.…”

“…BME was prepared from the Chinese variety of young bitter melons (raw and green) as discussed previously (12, 14). Briefly, BME was extracted using a household juicer and centrifuged at 560 × g at 4°C for 30 min, freeze dried at −45°C for 72 h and stored at −80°C.…”

“…We found that BME inhibits HNSCC cell proliferation through modulation of c-Met signaling in in vitro as well as in vivo using a xenograft model (12). We recently observed that BME treatment reduces the regulatory T cell (Treg) activity in a HNSCC syngeneic mouse model (14). NK cells display rapid and potent killing of hematological cancers (15).…”