Bitter Melon Prevents the Development of 4-NQO–Induced Oral Squamous Cell Carcinoma in an Immunocompetent Mouse Model by Modulating Immune Signaling

Abstract

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide, and tobacco is one of the most common factors for HNSCC of the oral cavity. We have previously observed that bitter melon () extract (BME) exerts antiproliferative activity against several cancers including HNSCC. In this study, we investigated the preventive role of BME in 4-nitroquinoline 1-oxide (4-NQO) carcinogen-induced HNSCC. We observed that BME feeding significantly reduced the incidence of 4-NQO-induced oral cancer in a mouse model. Histologic analysis suggested control 4-NQO-treated mouse tongues showed neoplastic changes ranging from moderate dysplasia to invasive squamous cell carcinoma, whereas no significant dysplasia was observed in the BME-fed mouse tongues. We also examined the global transcriptome changes in normal versus carcinogen-induced tongue cancer tissues, and following BME feeding. Gene ontology and pathway analyses revealed a signature of biological processes including "immune system process" that is significantly dysregulated in 4-NQO-induced oral cancer. We identified elevated expression of proinflammatory genes, s100a9, IL23a, IL1β and immune checkpoint gene PDCD1/PD1, during oral cancer development. Interestingly, BME treatment significantly reduced their expression. Enhancement of MMP9 ("ossification" pathway) was noted during carcinogenesis, which was reduced in BME-fed mouse tongue tissues. Our study demonstrates the preventive effect of BME in 4-NQO-induced carcinogenesis. Identification of pathways involved in carcinogen-induced oral cancer provides useful information for prevention strategies. Together, our data strongly suggest the potential clinical benefits of BME as a chemopreventive agent in the control or delay of carcinogen-induced HNSCC development and progression. .

Disrupting cholesterol esterification by bitter melon suppresses triple‐negative breast cancer cell growth

“…Several studies indicated potential importance of some dietary natural compounds for the treatment of aggressive cancers. Our and others previous studies have revealed that bitter melon extract (BME) exerts a strong anti‐cancer activity in several cancers including breast . Potential beneficial effect of bitter melon against lipid and glucose metabolic dysfunction has been reported .…”

Bioactivity-Guided Isolation of Neuritogenic Factor from the Seeds of the Gac Plant (Momordica cochinchinensis)

“…Several of species under Momordica have reported health benefits with most studies examining the charantia fruit which is commonly known as bitter melon, for its ability to antagonize diabetes [ 33 – 35 ], restore glucose homeostasis [ 36 ], enhance insulin secretion [ 37 ], protect islet beta-cells [ 38 ], and aid in healing of diabetic wounds [ 39 ]. Bitter melon has additional beneficial health-promoting properties on cardiovascular health [ 40 , 41 ], gastric ulcers, and can prevent angiogenesis, proliferation, and metastasis in diverse cancers [ 42 – 45 ]. Other species under the Momordica genus reportedly have similar health benefits both M .…”

Bitter Melon (Momordica Charantia), a Nutraceutical Approach for Cancer Prevention and Therapy

“…Further, in the syngenic model, the extract reduced infiltrating regulatory T (Treg) cell populations in the tumors and in spleens [43]. Subsequent studies showed continuous oral administration of water extract through drinking water (30% v/v) prevented 4-nitroquinoline 1-oxide (4-NQO)-induced mouse tongue squamous cell carcinoma development at the pre-neoplastic stages through modulation in proliferation, ossification, metabolism and immune system [41]. In nasopharyngeal carcinoma cells, the Bitter melon component alpha-momorcharin (α-MMC) showed cytotoxic activity on CNE-1 and HONE1 cells, whereas minimal effect was seen in non-cancerous human nasopharyngeal epithelial cells NP69 [13].…”