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The aim of this review was to provide the existing information regarding their cytotoxic activity, antitumor activity, as well as the proposed underlying mechanisms of action on various types of cancer. Fifty-nine eligible research articles retrieved from PubMed and ScienceDirect databases up to December 2018 are included in the analysis. The xanthone α-mangostin was the most widely studies compound. Most studies demonstrated promising cytotoxic activity of mangosteen extract and its isolated compounds, but investigation of their antitumor potential in animal models as well as in humans was limited. Further studies should be focused on their antitumor activity in animals and humans to support the clinical application of mangosteen for cancer chemotherapy and chemoprevention.
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Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, Bray F. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021;71(3):209-249.
Aisha AF, Abu-Salah KM, Ismail Z, Majid AM. In vitro and in vivo anti-colon cancer effects of Garcinia mangostana xanthones extract. BMC Complement Altern Med. 2012;12:104.
Sofowora A, Ogunbodede E, Onayade A. The role and place of medicinal plants in the strategies for disease prevention. Afr J Tradit Complement Altern Med. 2013;10(5):210-229.
Krajarng A, Nakamura Y, Suksamrarn S, Watanapokasin R. alpha-Mangostin induces apoptosis in human chondrosarcoma cells through downregulation of ERK/JNK and Akt signaling pathway. J Agric Food Chem. 2011;59(10):5746-5754.
Ee GC, Daud S, Izzaddin SA, Rahmani M. Garcinia mangostana: a source of potential anti-cancer lead compounds against CEM-SS cell line. J Asian Nat Prod Res. 2008;10(5-6):475-479.
Onodera T, Takenaka Y, Kozaki S, Tanahashi T, Mizushina Y. Screening of mammalian DNA polymerase and topoisomerase inhibitors from Garcinia mangostana L. and analysis of human cancer cell proliferation and apoptosis. Int J Oncol. 2016;48(3):1145-1154.
Han AR, Kim JA, Lantvit DD, Kardono LB, Riswan S, Chai H, et al. Cytotoxic xanthone constituents of the stem bark of Garcinia mangostana (mangosteen). J Nat Prod. 2009;72(11):2028-2031.
Moongkarndi P, Kosem N, Kaslungka S, Luanratana O, Pongpan N, Neungton N. Antiproliferation, antioxidation and induction of apoptosis by Garcinia mangostana (mangosteen) on SKBR3 human breast cancer cell line. J Ethnopharmacol. 2004;90(1):161-166.
Moongkarndi P, Jaisupa N, Samer J, Kosem N, Konlata J, Rodpai E, et al. Comparison of the biological activity of two different isolates from mangosteen. J Pharm Pharmacol. 2014;66(8):1171-1179.
Matsumoto K, Akao Y, Kobayashi E, Ohguchi K, Ito T, Tanaka T, et al. Induction of apoptosis by xanthones from mangosteen in human leukemia cell lines. J Nat Prod. 2003;66(8):1124-1127.
Suksamrarn S, Komutiban O, Ratananukul P, Chimnoi N, Lartpornmatulee N, Suksamrarn A. Cytotoxic prenylated xanthones from the young fruit of Garcinia mangostana. Chem Pharm Bull (Tokyo). 2006;54(3):301-305.
Balunas MJ, Su B, Brueggemeier RW, Kinghorn AD. Xanthones from the botanical dietary supplement mangosteen (Garcinia mangostana) with aromatase inhibitory activity. J Nat Prod. 2008;71(7):1161-1166.
Chang HF, Huang WT, Chen HJ, Yang LL. Apoptotic effects of gamma-mangostin from the fruit hull of Garcinia mangostana on human malignant glioma cells. Molecules. 2010;15(12):8953-8966.
Watanapokasin R, Jarinthanan F, Jerusalmi A, Suksamrarn S, Nakamura Y, Sukseree S, et al. Potential of xanthones from tropical fruit mangosteen as anticancer agents: caspase-dependent apoptosis induction in vitro and in mice. Appl Biochem Biotechnol. 2010;162 (4):1080-1094.
Wang JJ, Sanderson BJ, Zhang W. Cytotoxic effect of xanthones from pericarp of the tropical fruit mangosteen (Garcinia mangostana Linn.) on human melanoma cells. Food Chem Toxicol. 2011;49(9):2385-2391.
Chang HF, Wu CH, Yang LL. Antitumour and free radical scavenging effects of gamma-mangostin isolated from Garcinia mangostana pericarps against hepatocellular carcinoma cell. J Pharm Pharmacol. 2013;65(9):1419-1428.
Liu Z, Antalek M, Nguyen L, Li X, Tian X, Le A, et al. The effect of gartanin, a naturally occurring xanthone in mangosteen juice, on the mTOR pathway, autophagy, apoptosis, and the growth of human urinary bladder cancer cell lines. Nutr Cancer. 2013;65(Suppl 1):68-77.
Setiawan AS, Oewen RR, Supriatno, Soewondo W, Sidik, Supratman U. 8-hydroxycudraxanthone G suppresses IL-8 production in SP-C1 tongue cancer cells. Nat Prod Commun. 2014;9(1):75-78.
Xu Q, Ma J, Lei J, Duan W, Sheng L, Chen X, et al. Alpha-Mangostin suppresses the viability and epithelial-mesenchymal transition of pancreatic cancer cells by downregulating the PI3K/Akt pathway. Biomed Res Int. 2014;2014:546353.
Kim MO, Lee HS, Chin YW, Moon DO, Ahn JS. Gartanin induces autophagy through JNK activation which extenuates caspase-dependent apoptosis. Oncol Rep. 2015;34(1):139-146.
Seo KH, Ryu HW, Park MJ, Park KH, Kim JH, Lee MJ, et al. Mangosenone F, a furanoxanthone from Garciana mangostana, induces reactive oxygen species-mediated apoptosis in lung cancer cells and decreases xenograft tumor growth. Phytother Res. 2015;29(11):1753-1760.
Kim M, Chin YW, Lee EJ. Alpha, gamma-mangostins induce autophagy and show synergistic effect with gemcitabine in pancreatic cancer cell lines. Biomol Ther. 2017;25(6):609-617.
Luo M, Liu Q, He M, Yu Z, Pi R, Li M, et al. Gartanin induces cell cycle arrest and autophagy and suppresses migration involving PI3K/Akt/mTOR and MAPK signalling pathway in human glioma cells. J Cell Mol Med. 2017;21(1):46-57.
Yang R, Li P, Li N, Zhang Q, Bai X, Wang L, et al. Xanthones from the pericarp of Garcinia mangostana. Molecules. 2017;22(5):683.
Aukkanimart R, Boonmars T, Sriraj P, Sripan P, Songsri J, Ratanasuwan P, et al. In vitro and in vivo inhibitory effects of alpha-mangostin on cholangiocarcinoma cells and allografts. APJCP. 2017;18(3):707-713.
Chen JJ, Long ZJ, Xu DF, Xiao RZ, Liu LL, Xu ZF, et al. Inhibition of autophagy augments the anticancer activity of alpha-mangostin in chronic myeloid leukemia cells. Leuk Lymphoma. 2014;55(3):628-638.
Chitchumroonchokchai C, Thomas-Ahner JM, Li J, Riedl KM, Nontakham J, Suksumrarn S, et al. Anti-tumorigenicity of dietary alpha-mangostin in an HT-29 colon cell xenograft model and the tissue distribution of xanthones and their phase II metabolites. Mol Nutr Food Res. 2013;57(2):203-211.
Fazry S, Noordin MAM, Sanusi S, Noor MM, Aizat WM, Lazim AM, et al. Cytotoxicity and toxicity evaluation of xanthone crude extraction hypoxic human hepatocellular carcinoma and zebrafish (Danio rerio) embryos. Toxics. 2018;6(4):60.
Wang JJ, Shi QH, Zhang W, Sanderson BJ. Anti-skin cancer properties of phenolic-rich extract from the pericarp of mangosteen (Garcinia mangostana Linn.). Food Chem Toxicol. 2012;50(9):3004-3013.
Taokaew S, Nunkaew N, Siripong P, Phisalaphong M. Characteristics and anticancer properties of bacterial cellulose films containing ethanolic extract of mangosteen peel. J Biomater Sci Polym Ed. 2014;25(9):907-922.
Priya VV, Jainu M, Mohan SK. Biochemical Evidence for the antitumor potential of Garcinia mangostana Linn. on diethylnitro-samine-induced hepatic carcinoma. Pharmacogn Mag. 2018;14(54):186-190.
Moongkarndi P, Kosem N, Luanratana O, Jongsomboonkusol S, Pongpan N. Antipro-liferative activity of Thai medicinal plant extracts on human breast adenocarcinoma cell line. Fitoterapia. 2004;75(3-4):375-377.
Nabandith V, Suzui M, Morioka T, Kaneshiro T, Kinjo T, Matsumoto K, et al. Inhibitory effects of crude alpha-mangostin, a xanthone derivative, on two different categories of colon preneoplastic lesions induced by 1, 2-dimethylhydrazine in the rat. Asian Pac J Cancer Prev. 2004;5(4):433-438.
Li G, Petiwala SM, Nonn L, Johnson JJ. Inhibition of CHOP accentuates the apoptotic effect of α-mangostin from the mangosteen fruit (Garcinia mangostana) in 22Rv1 prostate cancer cells. Biochem Biophys Res Commun. 2014;453(1):75-80.
Li G, Petiwala SM, Pierce DR, Nonn L, Johnson JJ. Selective modulation of endoplasmic reticulum stress markers in prostate cancer cells by a standardized mangosteen fruit extract. PLoS One. 2013; 8(12):e81572.
Yu L, Zhao M, Yang B, Bai W. Immunomodulatory and anticancer activities of phenolics from Garcinia mangostana fruit pericarp. Food Chem. 2009;116(4):969-973
Xu Z, Huang L, Chen XH, Zhu XF, Qian XJ, Feng GK, et al. Cytotoxic prenylated xanthones from the pericarps of Garcinia mangostana. Molecules. 2014;19(2):1820-1827.
Mohamed GA, Al-Abd AM, El-Halawany AM, Abdallah HM, Ibrahim SRM. New xanthones and cytotoxic constituents from Garcinia mangostana fruit hulls against human hepatocellular, breast, and colorectal cancer cell lines. J Ethnopharmacol. 2017;198:302-312.
Xu XH, Liu QY, Li T, Liu JL, Chen X, Huang L, et al. Garcinone E induces apoptosis and inhibits migration and invasion in ovarian cancer cells. Sci Rep. 2017;7(1):10718.
Lee YJ, Jung O, Lee J, Son J, Cho JY, Ryou C, et al. Maclurin exerts anti-cancer effects on PC3 human prostate cancer cells via activation of p38 and inhibitions of JNK, FAK, AKT, and c-Myc signaling pathways. Nutr Res. 2018;58:62-71.
Fukuda M, Sakashita H, Hayashi H, Shiono J, Miyake G, Komine Y, et al. Synergism between α-mangostin and TRAIL induces apoptosis in squamous cell carcinoma of the oral cavity through the mitochondrial pathway. Oncol Rep. 2017;38(6):3439-3446.
Yuan J, Wu Y, Lu G. α-Mangostin suppresses lipopolysaccharide-induced invasion by inhibiting matrix metalloproteinase-2/9 and increasing E-cadherin expression through extracellular signal-regulated kinase signaling in pancreatic cancer cells. Oncol Lett. 2013;5(6):1958-1964.
Zhang C, Yu G, Shen Y. The naturally occurring xanthone α-mangostin induces ROS-mediated cytotoxicity in non-small scale lung cancer cells. Saudi J Biol Sci. 2018;25(6):1090-1095.
Wudtiwai B, Pitchakarn P, Banjerdpongchai R. Alpha-mangostin, an active compound in Garcinia mangostana, abrogates anoikis-resistance in human hepatocellular carcinoma cells. Toxicol In Vitro. 2018;53:222-232.
Nakagawa Y, Iinuma M, Naoe T, Nozawa Y, Akao Y. Characterized mechanism of alpha-mangostin-induced cell death: caspase-independent apoptosis with release of endonuclease-G from mitochondria and increased miR-143 expression in human colorectal cancer DLD-1 cells. Bioorg Med Chem. 2007;15(16):5620-5628.
Kritsanawong S, Innajak S, Imoto M, Watanapokasin R. Antiproliferative and apoptosis induction of α-mangostin in T47D breast cancer cells. Int J Oncol. 2016;48(5):2155-2165.
Kurose H, Shibata MA, Iinuma M, Otsuki Y. Alterations in cell cycle and induction of apoptotic cell death in breast cancer cells treated with α-mangostin extracted from mangosteen pericarp. J Biomed Biotechnol. 2012;2012:672428.
Shan T, Cui XJ, Li W, Lin WR, Lu HW, Li YM, et al. α-Mangostin suppresses human gastric adenocarcinoma cells in vitro via blockade of Stat3 signaling pathway. Acta Pharmacol Sin. 2014;35(8):1065-1073.
Wang JJ, Sanderson BJ, Zhang W. Significant anti-invasive activities of α-mangostin from the mangosteen pericarp on two human skin cancer cell lines. Anticancer Res. 2012;32(9):3805-3816.
Lee HN, Jang HY, Kim HJ, Shin SA, Choo GS, Park YS, et al. Antitumor and apoptosis-inducing effects of α-mangostin extracted from the pericarp of the mangosteen fruit (Garcinia mangostana L.)in YD-15 tongue mucoepidermoid carcinoma cells. Int J Mol Med. 2016;37(4):939-948.
Li P, Tian W, Ma X. Alpha-mangostin inhibits intracellular fatty acid synthase and induces apoptosis in breast cancer cells. Mol Cancer. 2014;13:138.
Scolamiero G, Pazzini C, Bonafè F, Guarnieri C, Muscari C. Effects of α-mangostin on viability, growth and cohesion of multicellular spheroids derived from human breast cancer cell lines. Int J Med Sci. 2018;15(1):23-30.
Matsumoto K, Akao Y, Yi H, Ohguchi K, Ito T, Tanaka T, et al. Preferential target is mitochondria in α-mangostin-induced apoptosis in human leukemia HL60 cells. Bioorg Med Chem. 2004; 12(22):5799-5806.
Hung SH, Shen KH, Wu CH, Liu CL, Shih YW. Alpha-mangostin suppresses PC-3 human prostate carcinoma cell metastasis by inhibiting matrix metalloproteinase-2/9 and urokinase-plasminogen expression through the JNK signaling pathway. J Agric Food Chem. 2009;57(4):1291-1298.
Wang F, Ma H, Liu Z, Huang W, Xu X, Zhang X. α-Mangostin inhibits DMBA/TPA-induced skin cancer through inhibiting inflammation and promoting autophagy and apoptosis by regulating PI3K/Akt/mTOR signaling pathway in mice. Biomed Pharmacother. 2017;92:672-680.
Cai N, Xie SJ, Qiu DB, Jia CC, Du C, Liu W, et al. Potential effects of α-mangostin in the prevention and treatment of hepato-cellular carcinoma. J Funct Foods. 2016;26:309-318.
Hafeez BB, Mustafa A, Fischer JW, Singh A, Zhong W, Shekhani MO, et al. α-Mangostin: a dietary antioxidant derived from the pericarp of Garcinia mangostana L. inhibits pancreatic tumor growth in xenograft mouse model. Antioxid Redox Signal. 2014;21(5):682-699.
Johnson JJ, Petiwala SM, Syed DN, Rasmussen JT, Adhami VM, Siddiqui IA, et al. α-Mangostin, a xanthone from mangosteen fruit, promotes cell cycle arrest in prostate cancer and decreases xenograft tumor growth. Carcinogenesis. 2012;33(2):413-419.
Fei X, Jo M, Lee B, Han SB, Lee K, Jung JK, et al. Synthesis of xanthone derivatives based on α-mangostin and their biological evaluation for anti-cancer agents. Bioorg Med Chem Lett. 2014;24(9):2062-2065.
Mizushina Y, Kuriyama I, Nakahara T, Kawashima Y, Yoshida H. Inhibitory effects of α-mangostin on mammalian DNA polymerase, topoisomerase, and human cancer cell proliferation. Food Chem Toxicol. 2013;59:793-800.
Chang HF, Yang LL. Gamma-mangostin, a micronutrient of mangosteen fruit, induces apoptosis in human colon cancer cells. Molecules. 2012;17(7):8010-8021.