Pomegranate extract mechanism in inhibiting the development of oral cancer: A review
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Background: Oral cancer is one of the most aggressive and invasive cancers with high metastatic potential. Oral cancer is cancer with the 11th highest number of cases in the world. Oral cancer is treated with chemotherapy and radiotherapy. However, this therapy causes side effects in the form of damage to normal cells in the surrounding tissue. Pomegranate extract contains polyphenols which may be great for inhibiting the development of oral cancer. Purpose: This article presents a systematic and comprehensive review of the potential of pomegranate extract as a natural product to inhibit the development of oral cancer. Review: Pomegranate extract was obtained by ethanol extraction using maceration method. The main content of pomegranate is polyphenolic compounds such as punicalagin, tannins, flavonoids, and ellagic acid. This compound reduces ATP formation, shortens the subG1 phase, and increases apoptosis. At the microcellular level, pomegranate extract can inhibit the activity of MMP-2 or MMP-9 to produce anti-proliferative, anti-angiogenesis and pro-apoptotic processes of cancer cells at concentrations of 25 and 50 μg/ml. Anti-proliferative and pro-apoptotic effects are produced through mitochondrial damage mechanisms. Exposure after 72 hours can reduce oral cell viability greater than exposure after 24 hours. Conclusion: Pomegranate extract is likely has four mechanisms to oral cancer: inhibiting the invasion, migration and growth of oral cancer cells, increasing oral cancer cell apoptosis and regulating antioxidant genes. So that this material can be used as a candidate for oral cancer therapy.
Budhy TI. Mengapa Terjadi Kanker. Edisi Kedua/Patobiologi. Surabaya: Airlangga Press; 2019. 1–27 p.
WHO. Oral Squamous Cell Carcinoma : Worldwide Prevalence. [Internet]. [Internet]. Available from: https://www.who.int/news-room/fact-sheets/detail/oral-health.
Indonesia KKR. Situasi Kesehatan Gigi dan Mulut 2019 [Internet]. Available from: https://www.kemkes.go.id/article/view/20030900005/situasi-kesehatan-gigi-dan-mulut-2019.html.
Gharat SA, Momin M, Bhavsar C. Oral Squamous Cell Carcinoma: Current Treatment Strategies and Nanotechnology-Based Approaches for Prevention and Therapy. Crit Rev Ther Drug Carrier Syst. 2016;33(4):363–400.
Grammatikopoulou MG, Gkiouras K, Papageorgiou SΤ, Myrogiannis I, Mykoniatis I, Papamitsou T, et al. Dietary Factors and Supplements Influencing Prostate Specific-Antigen (PSA) Concentrations in Men with Prostate Cancer and Increased Cancer Risk: An Evidence Analysis Review Based on Randomized Controlled Trials. Nutrients. 2020 Sep 29;12(10):2985.
Cicero AFG, Allkanjari O, Busetto GM, Cai T, Larganí G, Magri V, et al. Nutraceutical treatment and prevention of benign prostatic hyperplasia and prostate cancer. Arch Ital di Urol Androl organo Uff [di] Soc Ital di Ecogr Urol e Nefrol. 2019 Oct 2;91(3).
Zuniga KB, Chan JM, Ryan CJ, Kenfield SA. Diet and lifestyle considerations for patients with prostate cancer. Urol Oncol. 2020 Mar;38(3):105–17.
Wang L, Martins-Green M. Pomegranate and its components as alternative treatment for prostate cancer. Int J Mol Sci. 2014 Aug 25;15(9):14949–66.
Paller CJ, Pantuck A, Carducci MA. A review of pomegranate in prostate cancer. Prostate Cancer Prostatic Dis. 2017 Sep;20(3):265–70.
Li Y, Li S, Meng X, Gan R-Y, Zhang J-J, Li H-B. Dietary Natural Products for Prevention and Treatment of Breast Cancer. Nutrients. 2017 Jul 8;9(7):728.
Sturgeon SR, Ronnenberg AG. Pomegranate and breast cancer: possible mechanisms of prevention. Nutr Rev. 2010 Feb;68(2):122–8.
Zhou Y, Li Y, Zhou T, Zheng J, Li S, Li H-B. Dietary Natural Products for Prevention and Treatment of Liver Cancer. Nutrients. 2016 Mar 10;8(3):156.
Aiello P, Sharghi M, Mansourkhani SM, Ardekan AP, Jouybari L, Daraei N, et al. Medicinal Plants in the Prevention and Treatment of Colon Cancer. Oxid Med Cell Longev. 2019;2019:2075614.
Jaganathan SK, Vellayappan MV, Narasimhan G, Supriyanto E. Role of pomegranate and citrus fruit juices in colon cancer prevention. World J Gastroenterol. 2014 Apr 28;20(16):4618–25.
Philippou Y, Hadjipavlou M, Khan S, Rane A. Complementary and alternative medicine (CAM) in prostate and bladder cancer. BJU Int. 2013 Dec;112(8):1073–9.
Teniente SL, Flores-Gallegos AC, Esparza-González SC, Campos-Múzquiz LG, Nery-Flores SD, Rodríguez-Herrera R. Anticancer Effect of Pomegranate Peel Polyphenols against Cervical Cancer. Antioxidants. 2023 Jan 5;12(1):127.
Sirait AM. Faktor risiko tumor/kanker rongga mulut dan tenggorokan di Indonesia. Media Litbangkes. 2013;23(3):122–9.
Hrelec C. Management of Laryngeal Dysplasia and Early Invasive Cancer. Curr Treat Options Oncol. 2021 Aug 23;22(10):90.
Gale N, Blagus R, El-Mofty SK, Helliwell T, Prasad ML, Sandison A, et al. Evaluation of a new grading system for laryngeal squamous intraepithelial lesions--a proposed unified classification. Histopathology. 2014 Oct;65(4):456–64.
Wibowo IS, Priyanto W, Hardianto A. Karakteristik Karsinoma Sel Skuamosa Rongga Mulut di Rsup DR. Hasan Sadikin Bandung Periode Januari-Desember 2019. J Kedokt dan Kesehat Publ Ilm Fak Kedokt Univ Sriwij. 2022 Feb 17;9(1):97–102.
Zraik IM, HeíŸ-Busch Y. [Management of chemotherapy side effects and their long-term sequelae]. Urologe A. 2021 Jul;60(7):862–71.
Hardana H, Warganegara E. Ekstrak Buah Delima Sebagai Antibiotik Pengobatan Infeksi MRSA. Majority. 2015;4(9):83–7.
VuÄić V, Grabež M, Trchounian A, Arsić A. Composition and Potential Health Benefits of Pomegranate: A Review. Curr Pharm Des. 2019 Aug 23;25(16):1817–27.
Akhavan H, Barzegar M, Weidlich H, Zimmermann BF. Phenolic Compounds and Antioxidant Activity of Juices from Ten Iranian Pomegranate Cultivars Depend on Extraction. J Chem. 2015;2015:1–7.
Wong TL, Strandberg KR, Croley CR, Fraser SE, Nagulapalli Venkata KC, Fimognari C, et al. Pomegranate bioactive constituents target multiple oncogenic and oncosuppressive signaling for cancer prevention and intervention. Semin Cancer Biol. 2021 Aug;73:265–93.
Rafiq Z, Narasimhan S, Vennila R, Vaidyanathan R. Punigratane, a novel pyrrolidine alkaloid from Punica granatum rind with putative efflux inhibition activity. Nat Prod Res. 2016 Dec;30(23):2682–7.
Aruna P, Venkataramanamma D, Singh AK, Singh RP. Health Benefits of Punicic Acid: A Review. Compr Rev food Sci food Saf. 2016 Jan;15(1):16–27.
Peng S-Y, Hsiao C-C, Lan T-H, Yen C-Y, Farooqi AA, Cheng C-M, et al. Pomegranate extract inhibits migration and invasion of oral cancer cells by downregulating matrix metalloproteinase-2/9 and epithelial-mesenchymal transition. Environ Toxicol. 2020 Jun;35(6):673–82.
Cheshomi H, Bahrami AR, Rafatpanah H, Matin MM. The effects of ellagic acid and other pomegranate (Punica granatum L.) derivatives on human gastric cancer AGS cells. Hum Exp Toxicol. 2022;41:9603271211064534.
Liu H, Zeng Z, Wang S, Li T, Mastriani E, Li Q-H, et al. Main components of pomegranate, ellagic acid and luteolin, inhibit metastasis of ovarian cancer by down-regulating MMP2 and MMP9. Cancer Biol Ther. 2017 Dec 2;18(12):990–9.
Peng S-Y, Lin L-C, Chen S-R, Farooqi AA, Cheng Y-B, Tang J-Y, et al. Pomegranate Extract (POMx) Induces Mitochondrial Dysfunction and Apoptosis of Oral Cancer Cells. Antioxidants (Basel, Switzerland). 2021 Jul 13;10(7):1117.
Farhan M, Rizvi A, Ali F, Ahmad A, Aatif M, Malik A, et al. Pomegranate juice anthocyanidins induce cell death in human cancer cells by mobilizing intracellular copper ions and producing reactive oxygen species. Front Oncol. 2022;12:998346.
Hussein AM, El-Beih NM, Swellam M, El-Hussieny EA. Pomegranate juice and punicalagin-mediated chemoprevention of hepatocellular carcinogenesis via regulating miR-21 and NF-κB-p65 in a rat model. Cancer Cell Int. 2022 Nov 2;22(1):333.
Mukherjee S, Ghosh S, Choudhury S, Gupta P, Adhikary A, Chattopadhyay S. Pomegranate Polyphenols Attenuate Inflammation and Hepatic Damage in Tumor-Bearing Mice: Crucial Role of NF-κB and the Nrf2/GSH Axis. J Nutr Biochem. 2021 Nov;97:108812.
Wang XZ, Zhang SF, Yang ZH, Ye ZW, Liu J. Punicalagin suppresses osteosarcoma growth and metastasis by regulating NF-κB signaling. J Biol Regul Homeost Agents. 2020;34(5):1699–708.
Huang T, Zhang X, Wang H. Punicalagin inhibited proliferation, invasion and angiogenesis of osteosarcoma through suppression of NF"‘κB signaling. Mol Med Rep. 2020 Sep;22(3):2386–94.
Mandal A, Bhatia D, Bishayee A. Anti-Inflammatory Mechanism Involved in Pomegranate-Mediated Prevention of Breast Cancer: the Role of NF-κB and Nrf2 Signaling Pathways. Nutrients. 2017 Apr 28;9(5):436.
Li H-M, Kouye O, Yang D-S, Zhang Y-Q, Ruan J-Y, Han L-F, et al. Polyphenols from the Peels of Punica granatum L. and Their Bioactivity of Suppressing Lipopolysaccharide-Stimulated Inflammatory Cytokines and Mediators in RAW 264.7 Cells via Activating p38 MAPK and NF-κB Signaling Pathways. Molecules [Internet]. 2022 Jul 20;27(14):4622. Available from: http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC9318460
Elbakry MMM, ElBakary NM, Hagag SA, Hemida EHA. Pomegranate Peel Extract Sensitizes Hepatocellular Carcinoma Cells to Ionizing Radiation, Induces Apoptosis and Inhibits MAPK, JAK/STAT3, β-Catenin/NOTCH, and SOCS3 Signaling. Integr Cancer Ther. 2023;22:15347354221151020.
Lorzadeh E, Heidary Z, Mohammadi M, Nadjarzadeh A, Ramezani-Jolfaie N, Salehi-Abargouei A. Does pomegranate consumption improve oxidative stress? A systematic review and meta-analysis of randomized controlled clinical trials. Clin Nutr ESPEN. 2022 Feb;47:117–27.
Morsy RAA, Abbass EA, Hager EAA, Farid MH, Ellithy MM, Azmy A. Assessment of Anti-carcinogenic Effect of Pomegranate in Oral Squamous Cell Carcinoma (Pre-clinical Study). Pakistan J Biol Sci PJBS. 2019 Jan;22(12):580–4.
Bagheri M, Fazli M, Saeednia S, Kor A, Ahmadiankia N. Pomegranate peel extract inhibits expression of β-catenin, epithelial mesenchymal transition, and metastasis in triple negative breast cancer cells. Cell Mol Biol (Noisy-le-grand). 2018 May 30;64(7):86–91.
Nallanthighal S, Elmaliki KM, Reliene R. Pomegranate Extract Alters Breast Cancer Stem Cell Properties in Association with Inhibition of Epithelial-to-Mesenchymal Transition. Nutr Cancer. 2017 Oct;69(7):1088–98.
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