Mangiferin ve Kanser

Kanser, kontrolsüz ve anormal hücre çoğalması ile karakterize bir hastalıktır. Birçok yeni antikanser ilacı piyasada bulunmasına rağmen, çoğu zayıf biyoyararlanım, yüksek maliyet ve amaçlanmayan yan etkilerden dolayı hayati endişelere neden olmaktadır. Bu nedenle kanserin başka yöntemlerle önlenmesi düşüncesi ortaya atılmış ve “kemoprevensiyon” son yıllarda üzerinde en fazla çalışılan konulardan biri olmuştur. Mango olarak da bilinen Mangifera indica, uzun yıllardır Ayurveda ve geleneksel tıbbi sistemlerde kullanılmaktadır. Mangonun ana etken maddesi kabul edilen mangiferin, C-glukozilksanton yapıda çeşitli farmakolojik aktivitelere sahip, doğal bir polifenoldür. Son yıllarda yapılan çalışmalarda, mangiferinin antiinflamatuvar, antikanser, antidiyabetik, antioksidatif, yaşlanma karşıtı, immünomodülatör, hepatoprotektif, antihiperlipidemik, antialerjik ve analjezik etkiler gibi özelliklere sahip, umut verici bir antioksidan olduğu bildirilmiştir. In vitro ve in vivo çalışmalarda farklı kanser tiplerine karşı geniş spektrumlu etkililik göstermektedir. Mangiferinin yapısındaki C-glukozil bağ ve polihidroksi grupları, temel olarak serbest radikal temizleme etkinliğine katkıda bulunur. Ayrıca proinflamatuvar transkripsiyon etmenleri, hücre döngüsü proteinleri, büyüme faktörleri, kinazlar, sitokinler, kemokinler, adhezyon molekülleri ve inflamatuvar enzimleri modüle etme yeteneğine sahip olduğu gösterilmiştir. Bu hedefler potansiyel olarak kanserin başlatılması, ilerlemesi ve metastazını baskılayarak mangiferinin kemoprevensiyon ve tedavi edici etkilerine aracılık edebilir. Ancak, çalışmalarda mangiferinin oral biyoyararlılığının çok düşük olduğu bildirilmiş ve etkileri üzerine bildirilen çalışmalar ağırlıklı olarak kültür hücrelerinde ve kemirgenlerde yürütülmüştür. Mangiferinin daha iyi anlaşılabilmesi için insanlarda daha fazla klinik çalışmaya gerek vardır.

Mangiferin and Cancer

Cancer is a disease characterized by uncontrolled and abnormal cell proliferation. Although many new anticancer drugs are found in the market, most are causing vital concerns due to poor bioavailability, high cost and unintended side effects. For this reason, the idea of preventing cancer by other methods has been put forward and “chemoprevention” has become one of the most studied topics in recent years. Mangifera indica, also known as mango, is used for Ayurveda and traditional medical systems, for long years. Mangiferin, the main active ingredient of mango, is a natural polyphenol with various pharmacological activities in its C-glucoxanthone structure. In recent years studies; mangiferin has been reported to be a promising antioxidant with properties such as antiinflammatory, anticancer, antidiabetic, antioxidative, antiaging, immunomodulatory, hepatoprotective, antihyperlipidemic, antiallergic and analgesic effects. In vitro and in vivo studies show broad spectrum efficacy against different types of cancer. The C-glucosyl bond and polyhydroxy groups of the mangiferin structure are mainly responsible for the free radical cleansing activity. It has also been shown to have the ability to modulate proinflammatory transcription factors, cell cycle proteins, growth factors, kinases, cytokines, chemokines, adhesion molecules and inflammatory enzymes. These targets may potentially mediate chemoprevention and therapeutic effects of mangiferin by inhibiting the initiation, progression and metastasis of cancer. However, studies have reported that the oral bioavailability of mangiferin is very low, and the studies reported on their efficacy are predominantly carried out in culture cells and rodents. More clinical trials are needed in humans for better understanding of mangiferin.

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  • 1. American Cancer Society. Cancer Facts & Figures 2015. Atlanta, GA: American Cancer Society. https:// www.cancer.org/content/dam/cancer-org/research/ cancer-facts-and-statistics/annual-cancer-factsand- figures/2015/cancer-facts-and-figures-2015.pdf. Accessed June 24, 2015.
  • 2. Torre L, Bray F, Siegel R, Ferlay J, Lortet-Tieulent J, Jemal A. Global cancer statistics 2012. Cancer J. Clin. 2015;65:87–108.
  • 3. Weng CJ, Yen GC. Chemopreventive effects of dietary phytochemicals against cancer invasion and metastasis: Phenolic acids, monophenol, polyphenol, and their derivatives. Cancer Treat Rev. 2012; 38(1):76-87.
  • 4. Lee JH, Khor TO, Shu L, Su ZY, Fuentes F, Kong AN. Dietary phytochemicals and cancer prevention: Nrf2 signaling, epigenetics, and cell death mechanisms in blocking cancer initiation and prgression. Pharmacol Ther. 2013;137(2):153-71.
  • 5. Shah KA, Patel MB, Patel RJ, Parmar PK. Mangifera Indica (Mango) Pharmacogn Rev. 2010;4(7):42–8.
  • 6. Gold-Smith F, Fernandez A, Bishop K. Mangiferin and Cancer: Mechanisms of Action. Nutrients 2016;8:396.
  • 7. Rivera DG, Hernandez I, Merinos N, Luque Y, Alvarez A, Martin Y, et al. Mangifera indica L. extract (Vimang) and Mangiferin reduce the airway inflammation and Th2 cytokines in murine model of allergic asthma. J Pharm Pharmacol. 2011;63(10):1336-45.
  • 8. Ganogpichayagrai A, Palanuvej C, Ruangrungsi N. Antidiabetic and anticancer activities of Mangifera indica cv. Okrong leaves. J Adv Pharm Technol Res 2017;8(1): 19-24.
  • 9. Singh AK, Raj V, Keshari AK, Rai A, Kumar P, Rawat A, et al. Isolated Mangiferin and naringenin exert antidiabetic effect via PPARγ/GLUT4 dual agonistic action with strong metabolic regulation. Chem Biol Interact 2018;280:33-44.
  • 10. Wang H, Zhu YY, Wang L, Teng T, Zhou M, Wang SG, et al. Mangiferin ameliorates fatty liver via modulation of autophagy and inflammation in high-fat-diet induced mice. Biomed Pharmacother 2017;96:328-35.
  • 11. Sandoval-Gallegos EM, Ramírez-Moreno E, Lucio JG, Arias-Rico J, Cruz-Cansino N, Ortiz MI, Cariño-Cortés R. In vitro bioaccessibility and effect of Mangifera indica (Ataulfo) leaf extract on ınduced dyslipidemia. J Med Food 2018;21(1):47-56.
  • 12. Ishida M, Sasaki T, Nishi K, Tamamoto T, Sugahara T. Suppressive effect of ethanol extract from mango (Mangifera indica L.) peel on IgE production in vitro and in vivo. Biosci Biotechnol Biochem 2018;3:1-8.
  • 13. Núñez Sellés AJ, Dagila M, Rastrelli L. The potential role of Mangiferin in cancer treatment through its immunomodulatory, anti-angiogenic, apoptopic, and gene regulatory effects. Biofactors. 2016;42(5):475–91.
  • 14. Imran M, Arshad MS, Butt MS, Kwon JH, Arshad MU and Sultan MT. Mangiferin: a natural miracle bioactive compound against lifestyle related disorders. Lipids Health Dis. 2017;16(1):84.
  • 15. Singh SK, Sharma VK, Kumar Y, Sadish Kumar S, Sinha SK. Phytochemical and pharmacological investigations on Mangiferin. Herbapolonica 2009;55(1):126-39.
  • 16. Matkowski A, Kuś P, Góralska E, Woźniak D. Mangiferin - a bioactive xanthonoid, not only from mango and not just antioxidant. Mini Rev Med Chem 2013;13(3):439-55.
  • 17. Masibo M, He Q. Major mango polyphenols and their potential significance to human health. CRFSFS. 2008;7(4):309-19.
  • 18. Saha S, Sadhukhan P, Sil PC. Mangiferin: A xanthonoid with multipotent anti-inflammatory potential. BioFactors 2016;42(5):459–74.
  • 19. Rajendran P, Rengarajan T, Nandakumar N, Divya H, Nishigaki I. Mangiferin in cancer chemoprevention and treatment: pharmacokinetics and molecular targets. J Recept Signal Transduct Res. 2015;35(1):76-84.
  • 20. Mutlu Altundağ E, Yılmaz AM, Koçtürk S, Taga Y, Yalçın AS. Synergistic ınduction of apoptosis by quercetin and curcumin in chronic myeloid leukemia (K562) cells. Nutr Cancer 2018;70(1):97-108.
  • 21. Mehmood T, Maryam A, Tian X, Khan M, Ma T. Santamarine inhibits NF-кB and STAT3 activation and induces apoptosis in HepG2 liver cancer cells via oxidative stress. J Cancer 2017;8(18):3707–17.
  • 22. Sahoo BK, Zaidi AH, Gupta P, Mokhamatam RB, Raviprakash N, Mahali SK, et al. A natural xanthone increases catalase activity but decreases NF-kappa B and lipid peroxidation in U-937 and HepG2 cell lines. Eur J Pharmacol 2015;764:520-8.
  • 23. Takeda T, Tsubaki M, Kino T, Yamagishi M, Iida M, Itoh T, et al. Mangiferin induces apoptosis in multiple myeloma cell lines by suppressing the activation of nuclear factor kappa B-inducing kinase. Chem Biol Interact. 2016;251:26-33.
  • 24. Zhang QJ, Yue L. Inhıbıtory activity of mangiferin on Helicobacter pylori-induced inflammation in human gastric carcinoma Ags cells. Afr J Tradit Complement Altern Med 2017;14(1):263-71.
  • 25. Shi W, Deng J, Tong R, Yang Y, He X, Lv J, et al. Molecular mechanisms underlying Mangiferin-induced apoptosis and cell cycle arrest in A549 human lung carcinoma cells. Mol Med Rep. 2016;13:3423-32.
  • 26. Li J, Malakhova M, Mottamal M, Reddy K, Kurinov I, Carper A, et al. Norathyriol suppresses solar UVinduced skin cancer by targeting ERKs. Cancer Res 2012;72(1):260–70.
  • 27. Li M, Ma H, Yang L, Li P. Mangiferin inhibition of proliferation and induction of apoptosis in human prostate cancer cells is correlated with downregulation of B-cell lymphoma-2 and upregulation of microRNA-182. Oncol Lett. 2016;11: 817-22.
  • 28. Cuccioloni M, Bonfili L, Mozzicafreddo M, Cecarini V, Scuri S, Cocchioni M, et al. Mangiferin blocks proliferation and induces apoptosis of breast cancer cells via suppression of the mevalonate pathway and by proteasome inhibition. Food Funct 2016 ;7(10):4299-309.
  • 29. Li H, Huang J, Yang B, Xiang T, Yin X, Peng W, et al. Mangiferin exerts antitumor activity in breast cancer cells by regulating matrix metalloproteinases, epithelial to mesenchymal transition, and β catenin signaling pathway. Toxicol. Appl. Pharmacol 2013;272:180–90.
  • 30. Artavanis-Tsakonas S, Rand MD, Lake RJ. Notch signaling: cell fate control and signal integration in development. Science 1999;284(5415):770-6.
  • 31. Zou B, Wang H, Liu Y, Qi P, Lei T, Sun M, et al. Mangiferin induces apoptosis in human ovarian adenocarcinoma OVCAR3 cells via the regulation of Notch3. Oncol Rep 2017;38(3):1431-41.
  • 32. Peng ZG, Luo J, Xia LH, Chen Y, Song SJ. CML cell line K562 cell apoptosis induced by Mangiferin. Zhongguo Shi Yan Xue Ye Xue Za Zhi 2004;12(5):590-4.
  • 33. Shoji K, Tsubaki M, Yamazoe Y, Satou T, Itoh T, Kidera Y, et al. Mangiferin induces apoptosis by suppressing BclxL and XIAP expressions and nuclear entry of NF-κB in HL-60 cells. Arch Pharm Res. 2011;34(3):469–75.
  • 34. Barreto JC, Trevisan MT, Hull WE, Erben G, de Brito ES, Pfundstein B, et al. Characterization and quantitation of polyphenolic compounds in bark, kernel, leaves, and peel of mango (Mangifera indica L.). J Agric Food Chem 2008;56(14):5599-610.
  • 35. Luo F, Lv Q, Zhao Y, Hu G, Huang G, Zhang J, et al. Quantification and purification of Mangiferin from Chinese Mango (Mangifera indica L.) cultivars and its protective effect on human umbilical vein endothelial cells under H(2)O(2)-induced stress. Int J Mol Sci. 2012;13(9):11260-74.
  • 36. Das S, Nageshwar Rao B, Satish Rao BS. Mangiferin attenuates methylmercury induced cytotoxicity against IMR-32, human neuroblastoma cells by the inhibition of oxidative stress and free radical scavenging potential. Chem Biol Interact 2011;193(2):129-40.
  • 37. Agarwala S, Rao B N, Mudholkar K, Bhuwania R, Rao BSS. Mangiferin, a dietary xanthone protects against mercury-induced toxicity in HepG2 cells. Inc. Environ Toxicol 2012;27:117–27.
  • 38. Khurana RK, Kaur R, Lohan S, Singh KK, Singh B. Mangiferin: a promising anticancer bioactive. Pharm Pat Anal 2016;5(3):169-81.
  • 39. Zhang B, Zhao J, Li S, Zeng L, Chen Y, Fang J. Mangiferin activates the Nrf2-ARE pathway and reduces etoposideinduced DNA damage in human umbilical cord mononuclear blood cells. Pharm Biol. 2015;53(4):503-11.
  • 40. Rodeiro I, Delgado R, Garrido G. Effects of a Mangifera indica L. stem bark extract and Mangiferin on radiationinduced DNA damage in human lymphocytes and lymphoblastoid cells. Cell Prolif 2014;47(1):48-55.
  • 41. Xiao J, Liu L, Zhong Z, Xiao C, Zhang J. Mangiferin regulates proliferation and apoptosis in glioma cells by induction of microRNA-15b and inhibition of MMP-9 expression. Oncol Rep 2015;33(6):2815-20.
  • 42. Wilkinson AS, Taing MW, Pierson JT, Lin CN, Dietzgen RG, Shaw PN, et al. Estrogen modulation properties of Mangiferin and quercetin and the Mangiferin metabolite norathyriol. Food Funct 2015;6(6):1847–54.
  • 43. du Plessis-Stoman D , du Preez J, Van de Venter M . Combination treatment with oxaliplatin and Mangiferin causes increased apoptosis and downregulation of NFκB in cancer cell lines. Afr J Tradit Complement Altern Med. 2011;8(2):177-84.
  • 44. Zhang BP, Zhao J, Li SS, Yang LJ, Zeng LL, Chen Y, et al. Mangiferin activates Nrf2-antioxidant response element signaling without reducing the sensitivity to etoposide of human myeloid leukemia cells in vitro. Acta Pharmacol Sin. 2014;35(2):257-66.
  • 45. Koçyiğit A, Selek Ş. Eksojen antioksidanlar iki yönü keskin kılıçlardır. Bezmialem Science 2016;2:70-5.
  • 46. Han D, Chen C, Zhang C, Zhang Y, Tang X. Determination of mangiferin in rat plasma by liquid-liquid extraction with UPLC–MS/MS. J Pharm Biomed Anal. 2010; 1(1):260–63.
  • 47. Hou S, Wang F, Li Y, Li Y, Wang M, Sun D, et al. Pharmacokinetic study of Mangiferin in human plasma after oral administration. Food Chem. 2012;132(1):289- 94.
  • 48. Tian X, Xu Z, Li Z, Ma Y, Lian S, Guo X, et al. Pharmacokinetics of mangiferin and its metabolite— norathyriol, Part 2: Influence of UGT, CYP450, P-gp, and enterobacteria and the potential interaction in Rhizoma Anemarrhenae decoction with timosaponin B2 as the major contributor. Biofactors. 2016;42(5):545–55.
Beslenme ve Diyet Dergisi-Cover
  • ISSN: 1300-3089
  • Yayın Aralığı: Yılda 3 Sayı
  • Başlangıç: 1972
  • Yayıncı: Türkiye Diyestisyenler Derneği