Mangiferin and Cancer: Mechanisms of Action

Gold-Smith, Fuchsia; Fernandez, Alyssa; Bishop, Karen

doi:10.3390/nu8070396

Cited by 159Mangiferin and Mango ExtractsNatural Compound Pharmacology StudiesPineapple and bromelain studies

Mangiferin and Cancer: Mechanisms of Action

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Gold-Smith, Fuchsia, Fernandez, Alyssa, Bishop, Karen·2016·Nutrients

DOI 10.3390/nu8070396PMC PMC4963872

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Abstract

Mangiferin, a bioactive compound derived primarily from Anacardiaceae and Gentianaceae families and found in mangoes and honeybush tea, has been extensively studied for its therapeutic properties. Mangiferin has shown promising chemotherapeutic and chemopreventative potential. This review focuses on the effect of mangiferin on: (1) inflammation, with respect to NFκB, PPARү and the immune system; (2) cell cycle, the MAPK pathway G2/M checkpoint; (3) proliferation and metastasis, and implications on β-catenin, MMPs, EMT, angiogenesis and tumour volume; (4) apoptosis, with a focus on Bax/Bcl ratios, intrinsic/extrinsic apoptotic pathways and telomerase activity; (5) oxidative stress, through Nrf2/ARE signalling, ROS elimination and catalase activity; and (6) efficacy of chemotherapeutic agents, such as oxaliplatin, etoposide and doxorubicin. In addition, the need to enhance the bioavailability and delivery of mangiferin are briefly addressed, as well as the potential for toxicity.

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According to previous cancer-related experiments, MGF most consistently modulates four signaling axes: NF-κB, Nrf2, MAPK and PI3K/Akt.
“According to previous cancer-related experiments, MGF most consistently modulates four signaling axes that share common upstream triggers and downstream responses (38,39).”
From Mangiferin in human disease: Multifaceted mechanisms and applications (Review) (2026) · cites this paper as [38]
Sections 2.1, 2.2, 2.3 and 2.5 describe mangiferin’s effects on NF-κB, MAPK, Akt and Nrf2/ARE signaling, respectively. The paper does not establish that these are the four most consistently modulated axes, or that all four share common upstream triggers and downstream responses. The Akt evidence in section 2.3 concerns PMA-stimulated astroglioma cells. (LLM, conf=0.85)
Experimental — accuracy not yet measured
MAPK modulation by MGF is context dependent; a number of models show attenuation of ERK1/2, JNK and p38 phosphorylation, reduced AP-1 activity, and consequent decreases in proliferation and cytokine output.
“MAPK modulation is context dependent; a number of models show attenuation of ERK1/2, JNK and p38 phosphorylation, reduced activator protein (AP)-1 activity, and consequent decreases in proliferation and cytokine output (38,46).”
From Mangiferin in human disease: Multifaceted mechanisms and applications (Review) (2026) · cites this paper as [38]
Section 2.2.1 (page not provided) says mangiferin inhibits p38, ERK and JNK phosphorylation; Section 2.3.2 links it to reduced AP-1 binding in astroglioma cells. Section 2.1.1 reports reduced IL-6 and IL-8 production, but attributes that effect to NFκB downregulation. The paper does not establish the claimed chain from MAPK and AP-1 attenuation to reduced proliferation and cytokine output, or explicitly characterize MAPK modulation as context dependent. (LLM, conf=0.85)
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Multiparametric evaluation of the cytoprotective effect of the Mangifera indica L. stem bark extract and mangiferin in HepG2 cells
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Multifaceted Health Benefits of Mangifera indica L. (Mango): The Inestimable Value of Orchards Recently Planted in Sicilian Rural Areas
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Luteolin induces apoptotic cell death via antioxidant activity in human colon cancer cells
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Gallic Acid Content and an Antioxidant Mechanism Are Responsible for the Antiproliferative Activity of ‘Ataulfo’ Mango Peel on LS180 Cells
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Mango (Mangifera indicaL.): a magnificent plant with cancer preventive and anticancer therapeutic potential
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Mangiferin prevents diabetic nephropathy progression and protects podocyte function via autophagy in diabetic rat glomeruli
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Nrf2/HO-1 mediates the neuroprotective effect of mangiferin on early brain injury after subarachnoid hemorrhage by attenuating mitochondria-related apoptosis and neuroinflammation
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Mangiferin as New Potential Anti-Cancer Agent and Mangiferin-Integrated Polymer Systems—A Novel Research Direction
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Tropical Fruits and Their Co-Products as Bioactive Compounds and Their Health Effects: A Review
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Mangiferin Ameliorates Cisplatin Induced Acute Kidney Injury by Upregulating Nrf-2 via the Activation of PI3K and Exhibits Synergistic Anticancer Activity With Cisplatin
Sadhukhan, P., Saha, S., Dutta, S., & Sil, P. C. (2018) · Frontiers in Pharmacology · doi:10.3389/fphar.2018.00638 · Cited by 81 · see citing works
Bioactive Phenolic Compounds from the Agroindustrial Waste of Colombian Mango Cultivars ‘Sugar Mango’ and ‘Tommy Atkins’—An Alternative for Their Use and Valorization
Vargas, H. I. C., Ballesteros-Vivas, D., Barbosa, J. O., Morantes, S. J., Gutiérrez, F. A. A., & Parada‐Alfonso, F. (2019) · Antioxidants · doi:10.3390/antiox8020041 · Cited by 77 · see citing works
The combinatory effects of natural products and chemotherapy drugs and their mechanisms in breast cancer treatment
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Mitochondrial pyruvate carrier function determines cell stemness and metabolic reprogramming in cancer cells
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Coffee (Coffea arabica L.) by-Products as a Source of Carotenoids and Phenolic Compounds—Evaluation of Varieties With Different Peel Color
Esquivel, P., Viñas, M., Steingass, C. B., Gruschwitz, M., Guevara, E., Carle, R., Schweiggert, R. M., & Jiménez, V. M. (2020) · Frontiers in Sustainable Food Systems · doi:10.3389/fsufs.2020.590597 · Cited by 67 · see citing works
Complexity made easy: Aggregation‐induced emission small molecules for cancer diagnosis and phototherapies
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The Anti-Cancer Effect of Mangifera indica L. Peel Extract is Associated to γH2AX-mediated Apoptosis in Colon Cancer Cells
Lauricella, M., Galbo, V. L., Cernigliaro, C., Maggio, A., Piccionello, A. P., Calvaruso, G., Carlisi, D., Emanuele, S., Giuliano, M., & D’Anneo, A. (2019) · Antioxidants · doi:10.3390/antiox8100422 · Cited by 65 · see citing works
Prevention and treatment of cancer targeting chronic inflammation: research progress, potential agents, clinical studies and mechanisms
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Medicinal plants and bioactive natural products as inhibitors of NLRP3 inflammasome
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The effect of mangiferin on skin: Penetration, permeation and inhibition of ECM enzymes
Ochocka, R., Hering, A., Stefanowicz–Hajduk, J., Cal, K., & Barańska, H. (2017) · PLOS ONE · doi:10.1371/journal.pone.0181542 · Cited by 56 · see citing works
Metabolic profiling of four South African herbal teas using high resolution liquid chromatography-mass spectrometry and nuclear magnetic resonance
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Polyphenolic Characterization, Antioxidant, and Cytotoxic Activities of Mangifera indica Cultivars from Costa Rica
Navarro-Hoyos, M., Arnáez-Serrano, E., Moreira, I. M., Quesada, S., Azofeifa, G., Wilhelm-Romero, K., Vargas-Huertas, F., & Chen, P. C. (2019) · Foods · doi:10.3390/foods8090384 · Cited by 54 · see citing works
Mangiferin Attenuates LPS/D-GalN-Induced Acute Liver Injury by Promoting HO-1 in Kupffer Cells
Yang, S., Kuang, G., Zhang, L., Wu, S., Zhao, Z., Wang, B., Yin, X., Gong, X., & Wan, J. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.00285 · Cited by 53 · see citing works
Mangiferin ameliorates gestational diabetes mellitus-induced placental oxidative stress, inflammation and endoplasmic reticulum stress and improves fetal outcomes in mice
Sha, H., Zeng, H., Zhao, J. V., & Jin, H. (2019) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2019.172522 · Cited by 51 · see citing works
Suppressive activities of mangiferin on human epithelial ovarian cancer
Zeng, Z., Lin, C., Wang, S., Wang, P., Xu, W., Ma, W., Wang, J., Xiang, Q., Liu, Y., Yang, J., et al. (2020) · Phytomedicine · doi:10.1016/j.phymed.2020.153267 · Cited by 50 · see citing works
A novel PEGylated carbon nanotube conjugated mangiferin: An explorative nanomedicine for brain cancer cells
Harsha, P. J., Thotakura, N., Kumar, M., Sharma, S., Mittal, A., Khurana, R. K., Singh, B., Negi, P., & Raza, K. (2019) · Journal of Drug Delivery Science and Technology · doi:10.1016/j.jddst.2019.101186 · Cited by 49 · see citing works
Nutraceutical compounds: Echinoids, flavonoids, xanthones and caffeine identified and quantitated in the leaves of Coffea arabica trees from three regions of Brazil
de Almeida, R. F., Trevisan, M. T. S., Thomaziello, R. A., Breuer, A., Klika, K. D., Ulrich, C. M., & Owen, R. W. (2018) · Food Research International · doi:10.1016/j.foodres.2018.10.006 · Cited by 48 · see citing works
Mangiferin Ameliorates HFD-Induced NAFLD through Regulation of the AMPK and NLRP3 Inflammasome Signal Pathways
Yong, Z., Ruiqi, W., Hongji, Y., Ning, M., Chenzuo, J., Yu, Z., Zhixuan, X., Qiang, L., Qibing, L., Weiying, L., et al. (2021) · Journal of Immunology Research · doi:10.1155/2021/4084566 · Cited by 48 · see citing works
The role of inflammation in cadmium nephrotoxicity: NF-κB comes into view
Hassanein, E. H. M., Mohamed, W. R., Ahmed, O. S., Abdel‐Daim, M. M., & Sayed, A. M. M. (2022) · Life Sciences · doi:10.1016/j.lfs.2022.120971 · Cited by 47 · see citing works
Adhesive nanoparticles with inflammation regulation for promoting skin flap regeneration
Mao, X., Liu, L., Cheng, L., Cheng, R., Zhang, L., Deng, L., Sun, X., Zhang, Y., Sarmento, B., & Cui, W. (2019) · Journal of Controlled Release · doi:10.1016/j.jconrel.2019.01.031 · Cited by 45 · see citing works
Acute Effects of a Polyphenol-Rich Leaf Extract of Mangifera indica L. (Zynamite) on Cognitive Function in Healthy Adults: A Double-Blind, Placebo-Controlled Crossover Study
Wightman, E. L., Jackson, P. A., Forster, J. S., Khan, J., Wiebe, J. C., Gericke, N., & Kennedy, D. O. (2020) · Nutrients · doi:10.3390/nu12082194 · Cited by 45 · see citing works
In Vitro Gastrointestinal Digestion and Colonic Catabolism of Mango (Mangifera indica L.) Pulp Polyphenols
Ordóñez-Díaz, J. L., Moreno-Ortega, A., Roldán‐Guerra, F. J., Ortiz-Somovilla, V., Moreno‐Rojas, J. M., & Pereira‐Caro, G. (2020) · Foods · doi:10.3390/foods9121836 · Cited by 45 · see citing works
Gold Nanoparticles Synthesized Using Extracts of Cyclopia intermedia, Commonly Known as Honeybush, Amplify the Cytotoxic Effects of Doxorubicin
Aboyewa, J. A., Sibuyi, N. R. S., Meyer, M., & Oguntibeju, O. O. (2021) · Nanomaterials · doi:10.3390/nano11010132 · Cited by 43 · see citing works
Mangiferin: the miraculous xanthone with diverse pharmacological properties
Dutta, T., Das, T., Gopalakrishnan, A. V., Saha, S. C., Ghorai, M., Nandy, S., Kumar, M., Radha, Ghosh, A., Mukerjee, N., et al. (2023) · Naunyn-Schmiedeberg s Archives of Pharmacology · doi:10.1007/s00210-022-02373-6 · Cited by 45 · see citing works
Synthetic Chiral Derivatives of Xanthones: Biological Activities and Enantioselectivity Studies
Fernandes, C., Carraro, M. L., Ribeiro, J., Araújo, J., Tiritan, M. E., & Pinto, M. M. M. (2019) · Molecules · doi:10.3390/molecules24040791 · Cited by 42 · see citing works
SIRT1/PGC-1α signaling activation by mangiferin attenuates cerebral hypoxia/reoxygenation injury in neuroblastoma cells
Chen, M., Wang, Z., Zhou, W., Lu, C., Ji, T., Yang, W., Jin, Z., Tian, Y., Lei, W., Wu, S., et al. (2021) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2021.174236 · Cited by 40 · see citing works
Chinese Herbal Medicine-Based Cancer Therapy: Novel Anticancer Agents Targeting MicroRNAs to Regulate Tumor Growth and Metastasis
Peng, F., Xie, X., & Peng, C. Y. (2019) · The American Journal of Chinese Medicine · doi:10.1142/s0192415x19500873 · Cited by 39 · see citing works
Mangiferin enhances endochondral ossification‐based bone repair in massive bone defect by inducing autophagy through activating AMP‐activated protein kinase signaling pathway
Bai, Y., Liu, C., Fu, L., Gong, X., Dou, C., Cao, Z., Quan, H., Li, J., Kang, F., Dai, J., et al. (2018) · The FASEB Journal · doi:10.1096/fj.201701411r · Cited by 37 · see citing works
Neuroprotection of mangiferin against oxidative damage via arousing Nrf2 signaling pathway in PC12 cells
Peng, S., Hou, Y., Yao, J., & Fang, J. (2019) · BioFactors · doi:10.1002/biof.1488 · Cited by 37 · see citing works
An insight into in vitro antioxidant, antimicrobial, cytotoxic, and apoptosis induction potential of mangiferin, a bioactive compound derived from mangifera indica
Yehia, R. S., & Altwaim, S. A. (2023) · Plants · doi:10.3390/plants12071539 · Cited by 36 · see citing works
A review of antidiabetic active thiosugar sulfoniums, salacinol and neokotalanol, from plants of the genus Salacia
Morikawa, T., Ninomiya, K., Tanabe, G., Matsuda, H., Yoshikawa, M., & Muraoka, O. (2021) · Journal of Natural Medicines · doi:10.1007/s11418-021-01522-0 · Cited by 36 · see citing works
Unprecedented natural mangiferin excimer induced aggregation-induced emission luminogens for highly selective bioimaging of cancer cells
Long, R., Tang, C., Wei, Q., Tong, C., Tong, X., Shi, S., Guo, Y., & Yang, Y. (2021) · Sensors and Actuators B Chemical · doi:10.1016/j.snb.2021.130666 · Cited by 33 · see citing works
Mango leaf extract synthesized silver nanorods exert anticancer activity on breast cancer and colorectal carcinoma cells
Anoop, N. V., Jacob, R., Paulson, J. M., Dineshkumar, B., & Narayana, C. R. (2017) · Journal of Drug Delivery Science and Technology · doi:10.1016/j.jddst.2017.11.023 · Cited by 31 · see citing works
Nontoxic Glucomoringin-Isothiocyanate (GMG-ITC) Rich Soluble Extract Induces Apoptosis and Inhibits Proliferation of Human Prostate Adenocarcinoma Cells (PC-3)
Mohammed, J. S., Karim, N. A. A., Eliaser, E. M., Waziri, P. M., Ahmed, H., Barau, M. M., Kong, L., & Razis, A. F. A. (2018) · Nutrients · doi:10.3390/nu10091174 · Cited by 31 · see citing works
Characterization and screening of cyclooxygenase-2 inhibitors from Zi-shen pill by affinity ultrafiltration-ultra performance liquid chromatography mass spectrometry
Huai, J., Zhao, X., Wang, S., Xie, L., Li, Y., Zhang, T., Cheng, C., & Dai, R. (2019) · Journal of Ethnopharmacology · doi:10.1016/j.jep.2019.111900 · Cited by 30 · see citing works
Anti-angiogenic effects of mangiferin and mechanism of action in metastatic melanoma
Delgado-Hernández, R., Hernández-Balmaseda, I., Rodeiro-Guerra, I., Cesar Rodriguez Gonzalez, J., De Wever, O., Logie, E., Declerck, K., Pérez-Novo, C., & Vanden Berghe, W. (2020) · Melanoma Research · doi:10.1097/cmr.0000000000000647 · Cited by 29 · see citing works
Recent Formulation Advances of Mangiferin
Barakat, S., Nasr, M., Ahmed, R. F., Badawy, S., & Mortada, N. (2022) · Revista Brasileira de Farmacognosia · doi:10.1007/s43450-022-00297-z · Cited by 28 · see citing works
Modulation of the Canonical Wnt Signaling Pathway by Dietary Polyphenols, an Opportunity for Colorectal Cancer Chemoprevention and Treatment
Villota, H., Röthlisberger, S., & Pedroza-Díaz, J. (2021) · Nutrition and Cancer · doi:10.1080/01635581.2021.1884730 · Cited by 27 · see citing works
Xanthones: A Class of Heterocyclic Compounds with Anticancer Potential
Gul, S., Aslam, K., Pirzada, Q., Rauf, A., Khalil, A. A., Semwal, P., Bawazeer, S., Al-Awthan, Y. S., Bahattab, O. S., Al-Duais, M. A., et al. (2022) · Current Topics in Medicinal Chemistry · doi:10.2174/1568026622666220901145002 · Cited by 27 · see citing works
In-depth analysis of the chemical composition, pharmacological effects, pharmacokinetics, and patent history of mangiferin
Kaurav, M., Kanoujia, J., Gupta, M., Goyal, P., Pant, S., Rai, S., Sahu, K. K., Bhatt, P., & Ghai, R. (2023) · Phytomedicine Plus · doi:10.1016/j.phyplu.2023.100445 · Cited by 23 · see citing works
Therapeutic potential of bioactive phytoconstituents found in fruits in the treatment of non-alcoholic fatty liver disease: A comprehensive review
Pathak, M. P., Pathak, K., Saikia, R., Gogoi, U., Patowary, P., Chattopadhyay, P., & Das, A. (2023) · Heliyon · doi:10.1016/j.heliyon.2023.e15347 · Cited by 28 · see citing works
Mangiferin (mango) attenuates AOM-induced colorectal cancer in rat’s colon by augmentation of apoptotic proteins and antioxidant mechanisms
Abdul-Aziz Ahmed, K., Jabbar, A. A. J., Abdulla, M. A., Zuhair Alamri, Z., Ain Salehen, N., Abdel Aziz Ibrahim, I., Almaimani, G., Bamagous, G. A., Almaimani, R. A., Almasmoum, H. A., et al. (2024) · Scientific Reports · doi:10.1038/s41598-023-50947-y · Cited by 26 · see citing works
Current strategies for nonalcoholic fatty liver disease treatment (Review)
Sun, J., Jin, X., & Li, Y. (2024) · International Journal of Molecular Medicine · doi:10.3892/ijmm.2024.5412 · Cited by 24 · see citing works
Growth Inhibitory Effect of Mangiferin on Thyroid Cancer Cell Line TPC1
Zhang, L., & Wang, M. (2018) · Biotechnology and Bioprocess Engineering · doi:10.1007/s12257-018-0212-x · Cited by 24 · see citing works
Prospects of ultrasonically extracted food bioactives in the field of non-invasive biomedical applications – A review
Mounika, A., Ilangovan, B., Mandal, S., Yashwant, W. S., Gali, S. P., & Shanmugam, A. (2022) · Ultrasonics Sonochemistry · doi:10.1016/j.ultsonch.2022.106121 · Cited by 25 · see citing works
Transferrin-Modified Mangiferin-Loaded SLNs: Preparation, Characterization, and Application in A549 Lung Cancer Cell
Zhou, Q. X., Hou, K., & Fu, Z. (2022) · Drug Design Development and Therapy · doi:10.2147/dddt.s366531 · Cited by 23 · see citing works
Improving Aqueous Solubility of Natural Antioxidant Mangiferin through Glycosylation by Maltogenic Amylase from Parageobacillus galactosidasius DSM 18751
Wu, J., Ding, H., Wang, T., Tsai, Y.-L., Ting, H., & Chang, T. (2021) · Antioxidants · doi:10.3390/antiox10111817 · Cited by 23 · see citing works
Mangiferin offers protection against deleterious effects of pharmaceuticals, heavy metals, and environmental chemicals
Naraki, K., Rezaee, R., Mashayekhi‐Sardoo, H., Hayes, A. W., & Karimi, G. (2020) · Phytotherapy Research · doi:10.1002/ptr.6864 · Cited by 22 · see citing works
Mangiferin is a new potential antimalarial and anticancer drug for targeting serine hydroxymethyltransferase
Maenpuen, S., Mee-udorn, P., Pinthong, C., Athipornchai, A., Phiwkaow, K., Watchasit, S., Pimviriyakul, P., Rungrotmongkol, T., Tinikul, R., Leartsakulpanich, U., et al. (2023) · Archives of Biochemistry and Biophysics · doi:10.1016/j.abb.2023.109712 · Cited by 22 · see citing works
Role of Mangiferin in Management of Cancers through Modulation of Signal Transduction Pathways
Rahmani, A. H., Almatroudi, A., Allemailem, K. S., Alharbi, H. O. A., Alwanian, W. M., Alhunayhani, B. A., Algahtani, M., Theyab, A., Almansour, N. M., Algefary, A. N., et al. (2023) · Biomedicines · doi:10.3390/biomedicines11123205 · Cited by 22 · see citing works
Nanocrystals of Mangiferin Using Design Expert: Preparation, Characterization, and Pharmacokinetic Evaluation
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Authors: Gold-Smith, F., Fernandez, A., & Bishop, K.
Affiliations: University of Auckland (NZ)
Corresponding author: Bishop, Karen
ORCID: Bishop, Karen
Venue: Nutrients
Publisher: MDPI AG
Published: 2016-06-28
Volume: 8
Issue: 7
Pages: 396
ISSN: 2072-6643 (ISSN-L)
DOI: 10.3390/nu8070396
PMC: PMC4963872
OpenAlex: W2461997959
Cited by: 158
References: 98
Citations by year: 2026: 7 · 2025: 10 · 2024: 11 · 2023: 24 · 2022: 21 · 2021: 20 · 2020: 14 · 2019: 26 · 2018: 16 · 2017: 9
FWCI: 3.76
Type: journal article
Language: en
Open access: gold
doi.org
Licence: cc-by
creativecommons.org/licenses/by/4.0/ (vor)
Locations: Nutrients (publishedVersion, cc-by)
Europe PMC (PubMed Central) (publishedVersion, cc-by)
PubMed Central (publishedVersion, cc-by)
PubMed (publishedVersion)
DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
ResearchSpace (University of Auckland) (submittedVersion, cc-by)
Topics: Health Sciences › Medicine › Complementary and alternative medicine › Mangiferin and Mango Extracts
Life Sciences › Agricultural and Biological Sciences › Plant Science › Natural Compound Pharmacology Studies
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pineapple and bromelain studies
Keywords: mangiferin, cancer, chemoprevention, NF-κB, PPARγ, inflammation, cell cycle, MAPK signaling, G2/M checkpoint, metastasis, epithelial-mesenchymal transition, angiogenesis, apoptosis, telomerase, oxidative stress, reactive oxygen species, catalase, oxaliplatin, etoposide, doxorubicin, bioavailability, toxicity, mango, honeybush tea
MeSH terms: Animals, Antineoplastic Agents, Cell Cycle, Disease Models, Animal, Drug Synergism, Humans, Inflammation, Neoplasm Metastasis, Plant Extracts, Apoptosis, Oxidative Stress, Toxicity Tests, Anacardiaceae, Gentianaceae, Xanthones, Cell Line, Tumor

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