Diverse roles of bitter melon (Momordica charantia) in prevention of oral cancer

Abstract

Oral squamous cell carcinoma (OSCC) is one of the common lethal malignancies which is increasing rapidly in the world. Increasing risks from alcohol and tobacco habits, lack of early detection markers, lack of effective chemotherapeutic agents, recurrence and distant metastasis make the disease more complicated to manage. Laboratory-based studies and epidemiological studies indicate important roles of nutraceuticals to manage different cancers. The plant bitter melon (Momordica charantia) is a good source of nutrients and bio-active phytochemicals such as triterpenoids, triterpene glycosides, phenolic acids, flavonoids, lectins, sterols and proteins. The plant is widely grown in Asia, Africa, and South America. Bitter melon has traditionally been used as a folk medicine and Ayurvedic medicine in Asian culture to treat diseases such as diabetes, since ancient times. The crude extract and some of the isolated pure compounds of bitter melon show potential anticancer effects against different cancers. In this review, we shed light on its effect on OSCC. Bitter melon extract has been found to inhibit cell proliferation and metabolism, induce cell death and enhance the immune defense system in the prevention of OSCC in vitro and in vivo. Thus, bitter melon may be used as an attractive chemopreventive agent in progression towards OSCC clinical study.

Keywords

Bitter melon (Momordica charantia) / oral squamous cell carcinoma / signal transduction / cancer metabolism / immune system / cancer prevention

References

[1] Nagai H.Cancer prevention from the perspective of global cancer burden patterns..J Thorac Dis2017;9:448-51 PMCID:PMC5394024

[2] Hanahan D.The hallmarks of cancer..Cell2000;100:57-70

[3] Vogelstein B.Cancer genes and the pathways they control..Nat Med2004;10:789-99

[4] Lambert AW,Weinberg RA.Emerging Biological Principles of Metastasis..Cell2017;168:670-91 PMCID:PMC5308465

[5] Mahjour F,Shrestha N.Mechanism for oral tumor cell lysyl oxidase like-2 in cancer development: synergy with PDGF-AB..Oncogenesis2019;8:34 PMCID:PMC6513832

[6] Zhang L,Zhu XW.Long non-coding RNAs in Oral squamous cell carcinoma: biologic function, mechanisms and clinical implications..Mol Cancer2019;18:102 PMCID:PMC6535863

[7] Saraswat N,Pillay R,George A.Knowledge, attitudes and practices of general medical practitioners in developed countries regarding oral cancer: an integrative review..Fam Pract2020;37:592-605 PMCID:PMC7759340

[8] Coletta RD,Salo T.Grand Challenges in Oral Cancers..Front Oral Health2020;1:3

[9] Siegel RL,Jemal A.Cancer statistics, 2020..CA Cancer J Clin2020;70:7-30

[10] Ram H,Kumar H,Bhatt ML.Oral cancer: risk factors and molecular pathogenesis..J Maxillofac Oral Surg2011;10:132-7 PMCID:PMC3177522

[11] Williams HK.Molecular pathogenesis of oral squamous carcinoma..Mol Pathol2000;53:165-72 PMCID:PMC1186964

[12] Speight PM.Update on oral epithelial dysplasia and progression to cancer..Head Neck Pathol2007;1:61-6 PMCID:PMC2807503

[13] Ye Y,Lee JJ.Genetic variations in cell-cycle pathway and the risk of oral premalignant lesions..Cancer2008;113:2488-95 PMCID:PMC2577230

[14] Peltanova B,Masarik M.Effect of tumor microenvironment on pathogenesis of the head and neck squamous cell carcinoma: a systematic review..Mol Cancer2019;18:63 PMCID:PMC6441173

[15] Shih JW,Wu ATH.Long noncoding RNA LncHIFCAR/MIR31HG is a HIF-1alpha co-activator driving oral cancer progression..Nat Commun2017;8:15874 PMCID:PMC5489688

[16] Rao CV.Immunomodulatory effects of Momordica charantia extract in the prevention of oral cancer..Cancer Prev Res (Phila)2018;11:185-6

[17] Burgy M,Lefevre F.Cetuximab-carboplatin-5-fluorouracil regimen in elderly patients with recurrent or metastatic head and neck squamous-cell carcinoma: a French retrospective survey..Oncology2017;93:11-7

[18] Nishiyama K,Niinuma T.Screening for long noncoding RNAs associated with oral squamous cell carcinoma reveals the potentially oncogenic actions of DLEU1..Cell Death Dis2018;9:826 PMCID:PMC6070574

[19] Tan DSW,Leong HS.Long noncoding RNA EGFR-AS1 mediates epidermal growth factor receptor addiction and modulates treatment response in squamous cell carcinoma..Nat Med2017;23:1167-75

[20] Oyebode O,Chilton PJ.Use of traditional medicine in middle-income countries: a WHO-SAGE study..Health Policy Plan2016;31:984-91 PMCID:PMC5013777

[21] Safarzadeh E,Baradaran B.Herbal medicine as inducers of apoptosis in cancer treatment..Adv Pharm Bull2014;4:421-7 PMCID:PMC4213780

[22] Nerurkar P.Bitter melon: antagonist to cancer..Pharm Res2010;27:1049-53

[23] Jia S,Zhang F.Recent Advances in Momordica charantia: Functional Components and Biological Activities..Int J Mol Sci2017;18:2555 PMCID:PMC5751158

[24] Dandawate PR,Padhye SB.Bitter melon: a panacea for inflammation and cancer..Chin J Nat Med2016;14:81-100 PMCID:PMC5276711

[25] Raina K,Agarwal R.Promise of bitter melon (Momordica charantia) bioactives in cancer prevention and therapy..Semin Cancer Biol2016;40-41:116-29 PMCID:PMC5067200

[26] Sur S.Bitter melon (Momordica charantia), a nutraceutical approach for cancer prevention and therapy..Cancers (Basel)2020;12:2064 PMCID:PMC7464160

[27] Fang EF,Scheibye-Knudsen M,Wong JH.Emerging antitumor activities of the bitter melon (Momordica charantia)..Curr Protein Pept Sci2019;20:296-301 PMCID:PMC6486373

[28] Upadhyay A,Singh D.A Review on Salient Pharmacological Features of Momordica charantia..International J of Pharmacology2015;11:405-13

[29] Rajamoorthi A,Steele R.Bitter melon reduces head and neck squamous cell carcinoma growth by targeting c-Met signaling..PLoS One2013;8:e78006 PMCID:PMC3798549

[30] Bhattacharya S,Steele R,Ray RB.Immunomodulatory role of bitter melon extract in inhibition of head and neck squamous cell carcinoma growth..Oncotarget2016;7:33202-9 PMCID:PMC5078086

[31] Duarte S,Momier D.Isolation of head and neck squamous carcinoma cancer stem-like cells in a syngeneic mouse model and analysis of hypoxia effect..Oncol Rep2012;28:1057-62

[32] Sominski DD,Brosnan K.Development of a squamous cell carcinoma mouse model for immunotoxicity testing..J Immunotoxicol2016;13:226-34

[33] Wang Z,Allevato MM.Syngeneic animal models of tobacco-associated oral cancer reveal the activity of in situ anti-CTLA-4..Nat Commun2019;10:5546 PMCID:PMC6895221

[34] Li H,Liu Y.Comprehensive exome analysis of immunocompetent metastatic head and neck cancer models reveals patient relevant landscapes..Cancers (Basel)2020;12:2935 PMCID:PMC7601118

[35] Sur S,Aurora R,Schwetye KE.Bitter melon prevents the development of 4-NQO-induced oral squamous cell carcinoma in an immunocompetent mouse model by modulating immune signaling..Cancer Prev Res (Phila)2018;11:191-202 PMCID:PMC5882513

[36] Hsiao PC,Hwang SY.Antiproliferative and hypoglycemic cucurbitane-type glycosides from the fruits of Momordica charantia..J Agric Food Chem2013;61:2979-86

[37] Liaw CC,Hsiao PC.5beta,19-epoxycucurbitane triterpenoids from Momordica charantia and their anti-inflammatory and cytotoxic activity..Planta Med2015;81:62-70

[38] Todd R,Munger K.Cell cycle dysregulation in oral cancer..Crit Rev Oral Biol Med2002;13:51-61

[39] Visconti R,Grieco D.Cell cycle checkpoint in cancer: a therapeutically targetable double-edged sword..J Exp Clin Cancer Res2016;35:153 PMCID:PMC5037895

[40] Ray RB,Steele R.Bitter melon (Momordica charantia) extract inhibits breast cancer cell proliferation by modulating cell cycle regulatory genes and promotes apoptosis..Cancer Res2010;70:1925-31

[41] Ru P,Nerurkar PV,Ray RB.Bitter melon extract impairs prostate cancer cell-cycle progression and delays prostatic intraepithelial neoplasia in TRAMP model..Cancer Prev Res (Phila)2011;4:2122-30 PMCID:PMC3232292

[42] Martin GS.Cell signaling and cancer..Cancer Cell2003;4:167-74

[43] Zhang Y,Jin K.Function of the c-Met receptor tyrosine kinase in carcinogenesis and associated therapeutic opportunities..Mol Cancer2018;17:45 PMCID:PMC5817860

[44] Arnold L,Thomas SM.Activated HGF-c-Met Axis in Head and Neck Cancer..Cancers (Basel)2017;9:169 PMCID:PMC5742817

[45] Chen Q,Fu C.The independence of and associations among apoptosis, autophagy, and necrosis..Signal Transduct Target Ther2018;3:18 PMCID:PMC6026494

[46] Ferreira CG,Kruyt FA.Apoptosis: target of cancer therapy..Clin Cancer Res2002;8:2024-34

[47] Sur S,Flaveny C.Inhibition of the key metabolic pathways, glycolysis and lipogenesis, of oral cancer by bitter melon extract..Cell Commun Signal2019;17:131 PMCID:PMC6802351

[48] Warburg O,Negelein E.The Metabolism of Tumors in the Body..J Gen Physiol1927;8:519-30 PMCID:PMC2140820

[49] Beloribi-Djefaflia S,Guillaumond F.Lipid metabolic reprogramming in cancer cells..Oncogenesis2016;5:e189 PMCID:PMC4728678

[50] Bhattacharya S,Steele R,Ray RB.Bitter melon enhances natural killer-mediated toxicity against head and neck cancer cells..Cancer Prev Res (Phila)2017;10:337-44 PMCID:PMC5499682

[51] Fang WY,Hsiao JR.Elevated S100A9 expression in tumor stroma functions as an early recurrence marker for early-stage oral cancer patients through increased tumor cell invasion, angiogenesis, macrophage recruitment and interleukin-6 production..Oncotarget2015;6:28401-24 PMCID:PMC4695068

[52] Markowitz J.Review of S100A9 biology and its role in cancer..Biochim Biophys Acta2013;1835:100-9 PMCID:PMC3670606

[53] Srikrishna G.S100A8 and S100A9: new insights into their roles in malignancy..J Innate Immun2012;4:31-40 PMCID:PMC3250655

[54] Mark R,Bierhaus A,Angel P.The receptor for advanced glycation end products is dispensable in a mouse model of oral and esophageal carcinogenesis..Histol Histopathol2013;28:1585-94

[55] Economopoulou P,Giotakis EI.The emerging role of immunotherapy in head and neck squamous cell carcinoma (HNSCC): anti-tumor immunity and clinical applications..Ann Transl Med2016;4:173 PMCID:PMC4876265

[56] Bhatia A.Novel molecular targets for chemoprevention in malignancies of the head and neck..Cancers (Basel)2017;9:113 PMCID:PMC5615328