Immunomodulatory role of bitter melon extract in inhibition of head and neck squamous cell carcinoma growth.
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.
Department of Pathology, Saint Louis University, Saint Louis, Missouri, USA.
Sourav
S
Bhattacharya
Department of Pathology, Saint Louis University, Saint Louis, Missouri, USA.
Naoshad
N
Muhammad
Department of Pathology, Saint Louis University, Saint Louis, Missouri, USA.
Robert
R
Steele
Department of Internal Medicine, Saint Louis University, Saint Louis, Missouri, USA.
Guangyong
G
Peng
Department of Pathology, Saint Louis University, Saint Louis, Missouri, USA.|Department of Internal Medicine, Saint Louis University, Saint Louis, Missouri, USA.
Ratna B
RB
Ray
D000818:Animals; D000074322:Antineoplastic Agents, Immunological / Q000302:isolation & purification / Q000494:pharmacology*; D000972:Antineoplastic Agents, Phytogenic / Q000302:isolation & purification / Q000494:pharmacology*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D016246:Lymphocytes, Tumor-Infiltrating / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D008809:Mice, Inbred C3H; D029777:Momordica charantia / Q000737:chemistry*; D008517:Phytotherapy; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology*; D010946:Plants, Medicinal; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D000077195:Squamous Cell Carcinoma of Head and Neck; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D013997:Time Factors; D047368:Tumor Burden / Q000187:drug effects; D019139:Tumor Escape; D059016:Tumor Microenvironment
D000074322:Antineoplastic Agents, Immunological; D000972:Antineoplastic Agents, Phytogenic; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; C489428:Myc protein, mouse; D010936:Plant Extracts; D018809:Proliferating Cell Nuclear Antigen; D016271:Proto-Oncogene Proteins c-myc
HNSCC; TME; bitter melon