Anticarcinogenic Effects of α-Mangostin: A Review

Kuo-jun Zhang; Qin-lan Gu; Kan Yang; Xian-jun Ming; Jin-xin Wang

doi:10.1055/s-0042-119651

Planta Medica, Inhaltsverzeichnis

Planta Med 2017; 83(03/04): 188-202
DOI: 10.1055/s-0042-119651

Reviews

Georg Thieme Verlag KG Stuttgart · New York

Anticarcinogenic Effects of α-Mangostin: A Review

Kuo-jun Zhang

¹Key Laboratory of Drug Design and Optimization of Jiangsu Province, China Pharmaceutical University, Nanjing, China

,

Qin-lan Gu

²Higher Vocational and Technical College, China Pharmaceutical University, Nanjing, China

,

Kan Yang

¹Key Laboratory of Drug Design and Optimization of Jiangsu Province, China Pharmaceutical University, Nanjing, China

,

Xian-jun Ming

¹Key Laboratory of Drug Design and Optimization of Jiangsu Province, China Pharmaceutical University, Nanjing, China

,

Jin-xin Wang

¹Key Laboratory of Drug Design and Optimization of Jiangsu Province, China Pharmaceutical University, Nanjing, China

› Institutsangaben

Abstract

Cancer chemoprevention is a promising strategy taken to block, reverse, or retard carcinogenesis. α-Mangostin, a natural xanthone isolated from the pericarps of mangosteen, represents one of the most studied chemopreventive agents. This compound has been reported to interfere with all the major stages of carcinogenesis: initiation, promotion, and progression. A number of mechanisms have been proposed for its anticarcinogenic activities. This review summarizes the current knowledge on the mechanisms that contribute to the observed activity of α-mangostin related to (i) modulation of carcinogenic biotransformation and mitigation of oxidative damage, (ii) induction of growth arrest and apoptosis, (iii) suppression of angiogenesis and metastasis, and (iv) combination with clinical chemotherapy drugs enhancing their efficacy and decreasing the toxic side effects. In addition, pharmacokinetic and toxicological studies of α-mangostin have also been highlighted in this review. Despite an overwhelming amount of knowledge in preclinical studies, there was almost no translation of α-mangostin into the clinic. It is hoped that continuous extensive and profound research will lead to the application of α-mangostin from experimental studies to evidence-based, clinically applicable pharmacotherapy.

Key words

α-mangostin - Clusiaceae - Garcinia mangostana - molecular mechanism - pharmacokinetics - toxicology

Volltext

Referenzen

References
1 El-Gamal MI, Oh CH. Synthesis, in vitro antiproliferative activity, and in silico studies of fused tricyclic coumarin sulfonate derivatives. Eur J Med Chem 2014; 84: 68-76
2 Kasala ER, Bodduluru LN, Madana RM, V AK, Gogoi R, Barua CC. V AK. Chemopreventive and therapeutic potential of chrysin in cancer: mechanistic perspectives. Toxicol Lett 2015; 233: 214-225
3 Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D, Bray F. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer 2015; 136: E359-E386
4 Singh SR. Cancer stem cells: recent developments and future prospects. Cancer Lett 2013; 338: 1-2
5 Mahapatra DK, Bharti SK, Asati V. Anti-cancer chalcones: Structural and molecular target perspectives. Eur J Med Chem 2015; 98: 69-114
6 Neergheen VS, Bahorun T, Taylor EW, Jen LS, Aruoma OI. Targeting specific cell signaling transduction pathways by dietary and medicinal phytochemicals in cancer chemoprevention. Toxicology 2010; 278: 229-241
7 Wu X, Patterson S, Hawk E. Chemoprevention–history and general principles. Best Pract Res Clin Gastroenterol 2011; 25: 445-459
8 Russo M, Spagnuolo C, Tedesco I, Russo GL. Phytochemicals in cancer prevention and therapy: truth or dare?. Toxins (Basel) 2010; 2: 517-551
9 Aggarwal BB, Shishodia S. Molecular targets of dietary agents for prevention and therapy of cancer. Biochem Pharmacol 2006; 71: 1397-1421
10 Wattenberg LW. Chemoprevention of cancer. Cancer Res 1985; 45: 1-8
11 Pedraza-Chaverri J, Cardenas-Rodriguez N, Orozco-Ibarra M, Perez-Rojas JM. Medicinal properties of mangosteen (Garcinia mangostana). Food Chem Toxicol 2008; 46: 3227-3239
12 Garrity AR, Morton GA, Morton JC. Nutraceutical mangosteen composition. US Patent 6730333 B1, 2004
13 Yeung S. Mangosteen for the cancer patient: facts and myths. J Soc Integr Oncol 2006; 4: 130-134
14 Shan T, Ma Q, Guo K, Liu J, Li W, Wang F, Wu E. Xanthones from mangosteen extracts as natural chemopreventive agents: potential anticancer drugs. Curr Mol Med 2011; 11: 666-677
15 Ibrahim MY, Hashim NM, Mariod AA, Mohan S, Abdulla MA, Abdelwahab SI, Arbab IA. α-Mangostin from Garcinia mangostana Linn: an updated review of its pharmacological properties. Arab J Chem 2016; 3: 317-329
16 Kwon KH, Barve A, Yu S, Huang MT, Kong ANT. Cancer chemoprevention by phytochemicals: potential molecular targets, biomarkers and animal models. Acta Pharmacol Sin 2007; 28: 1409-1421
17 Arakaki J, Sunagawa N, Chiba I, Morita N, Kinjo T, Kaneshiro T, Morioka T, Nishimaki T, Yoshimi N. Inhibitory effect of α-mangostin on colon carcinogenesis induced by azoxymethane plus dextran sulfate sodium in CD1 (ICR) mice. Cancer Res 2007; 67: Abstract 4974
18 Nabandith V, Suzui M, Morioka T, Kaneshiro T, Kinjo T, Matsumoto K, Akao Y, Iinuma M, Yoshimi N. Inhibitory effects of crude α-mangostin, a xanthone derivative, on two different categorie of colon preneoplastic lesions induced by 1, 2-dimethylhydrazine in the rat. Asian Pac J Cancer Prev 2004; 5: 433-438
19 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
20 Chitchumroonchokchai C, Thomas-Ahner JM, Li J, Riedl KM, Nontakham J, Suksumrarn S, Clinton SK, Kinghorn AD, Failla ML. 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: 203-211
21 Johnson JJ, Petiwala SM, Syed DN, Rasmussen JT, Adhami VM, Siddiqui IA, Kohl AM, Mukhtar H. alpha-Mangostin, a xanthone from mangosteen fruit, promotes cell cycle arrest in prostate cancer and decreases xenograft tumor growth. Carcinogenesis 2012; 33: 413-419
22 Hsieh SC, Huang MH, Cheng CW, Hung JH, Yang SF, Hsieh YH. α-Mangostin induces mitochondrial dependent apoptosis in human hepatoma SK-Hep-1 cells through inhibition of p 38 MAPK pathway. Apoptosis 2013; 18: 1548-1560
23 Lee HN, Jang HY, Kim HJ, Shin SA, Choo GS, Park YS, Kim SK, Jung JY. 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: 939-948
24 Chao AC, Hsu YL, Liu CK, Kuo PL. α-Mangostin, a dietary xanthone, induces autophagic cell death by activating the AMP-activated protein kinase pathway in glioblastoma cells. J Argric Food Chem 2011; 59: 2086-2096
25 Hafeez BB, Mustafa A, Fischer JW, Singh A, Zhong W, Shekhani MO, Meske L, Havighurst T, Kim K, Verma AK. 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: 682-699
26 Hafeez BB, Fischer JW, Mustafa A, Zhong W, Verma AK. α-Mangostin, a dietary xanthone, inhibits ectopic xenograft growth of pancreatic cancer cells in an athymic nude mice. Cancer Res 2012; 72: Abstract 5418
27 Shibata MA, Iinuma M, Morimoto J, Kurose H, Akamatsu K, Okuno Y, Akao Y, Otsuki Y. α-Mangostin extracted from the pericarp of the mangosteen (Garcinia mangostana Linn.) reduces tumor growth and lymph node metastasis in an immunocompetent xenograft model of metastatic mammary cancer carrying a p 53 mutation. BMC Med 2011; 9: 69
28 Lee JS, Surh YJ. Nrf2 as a novel molecular target for chemoprevention. Cancer Lett 2005; 224: 171-184
29 Klaunig JE, Kamendulis LM. The role of oxidative stress in carcinogenesis. Annu Rev Pharmacol Toxicol 2004; 44: 239-267
30 Aggarwal BB, Shishodia S, Sandur SK, Pandey MK, Sethi G. Inflammation and cancer: how hot is the link?. Biochem Pharmacol 2006; 72: 1605-1621
31 Signorelli P, Ghidoni R. Resveratrol as an anticancer nutrient: molecular basis, open questions and promises. J Nutr Biochem 2005; 16: 449-466
32 Jung HA, Su BN, Keller WJ, Mehta RG, Kinghorn AD. Antioxidant xanthones from the pericarp of Garcinia mangostana (Mangosteen). J Agric Food Chem 2006; 54: 2077-2082
33 Shou M, Korzekwa KR, Krausz KW, Buters J, Grogan J, Goldfarb I, Hardwick JP, Gonzalez FJ, Gelboin HV. Specificity of cDNA-expressed human and rodent cytochrome P450 s in the oxidative metabolism of the potent carcinogen 7, 12-dimethylbenz [a] anthracene. Mol Carcinog 1996; 17: 241-249
34 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: 1161-1166
35 Reyes-Fermin LM, Gonzalez-Reyes S, Tarco-Alvarez NG, Hernandez-Nava M, Orozco-Ibarra M, Pedraza-Chaverri J. Neuroprotective effect of α-mangostin and curcumin against iodoacetate-induced cell death. Nutr Neurosci 2012; 15: 34-41
36 Yu BP. Cellular defenses against damage from reactive oxygen species. Physiol Rev 1994; 74: 139-162
37 Ma Q. Transcriptional responses to oxidative stress: pathological and toxicological implications. Pharmacol Ther 2010; 125: 376-393
38 Devi Sampath P, Vijayaraghavan K. Cardioprotective effect of α-mangostin, a xanthone derivative from mangosteen on tissue defense system against isoproterenol-induced myocardial infarction in rats. J Biochem Mol Toxicol 2007; 21: 336-339
39 Sampath PD, Kannan V. Mitigation of mitochondrial dysfunction and regulation of eNOS expression during experimental myocardial necrosis by alpha-mangostin, a xanthonic derivative from Garcinia mangostana . Drug Chem Toxicol 2009; 32: 344-352
40 Buelna-Chontal M, Correa F, Hernández-Reséndiz S, Zazueta C, Pedraza-Chaverri J. Protective effect of α-mangostin on cardiac reperfusion damage by attenuation of oxidative stress. J Med Food 2011; 14: 1370-1374
41 Márquez-Valadez B, Lugo-Huitrón R, Valdivia-Cerda V, Miranda-Ramírez LR, Pérez-De La Cruz V, González-Cuahutencos O, Rivero-Cruz I, Mata R, Santamaría A, Pedraza-Chaverrí J. The natural xanthone α-mangostin reduces oxidative damage in rat brain tissue. Nutr Neurosci 2009; 12: 35-42
42 Yoshikawa M, Harada E, Miki A, Tsukamoto K, Liang S, Yamahara J, Murakami N. Antioxidant constituents from the fruit hulls of mangosteen (Garcinia mangostana L.) originating in Vietnam. Yakugaku Zasshi 1994; 114: 129-133
43 Fan CT, Su J. Antioxidative mechanism of isolated componentss from methanol extract of fruit hulls of Garcinia mongostana L. J Chinese Agr Chem Soc 1997; 35: 540-551
44 Williams P, Ongsakul M, Proudfoot J, Croft K, Beilin L. Mangostin inhibits the oxidative modification of human low density lipoprotein. Free Radic Res 1995; 23: 175-184
45 Mahabusarakam W, Proudfoot J, Taylor W, Croft K. Inhibition of lipoprotein oxidation by prenylated xanthones derived from mangostin. Free Radic Res 2000; 33: 643-659
46 Pedraza-Chaverri J, Reyes-Fermin LM, Nolasco-Amaya EG, Orozco-Ibarra M, Medina-Campos ON, Gonzalez-Cuahutencos O, Rivero-Cruz I, Mata R. ROS scavenging capacity and neuroprotective effect of alpha-mangostin against 3-nitropropionic acid in cerebellar granule neurons. Exp Toxicol Pathol 2009; 61: 491-501
47 Sun D, Zhang S, Wei Y, Yin L. Antioxidant activity of mangostin in cell-free system and its effect on K562 leukemia cell line in photodynamic therapy. Acta Biochim Biophys Sin 2009; 41: 1033-1043
48 Cui J, Hu W, Cai Z, Liu Y, Li S, Tao W, Xiang H. New medicinal properties of mangostins: analgesic activity and pharmacological characterization of active ingredients from the fruit hull of Garcinia mangostana L. Pharmacol Biochem Behav 2010; 95: 166-172
49 Martínez A, Galano A, Vargas R. Free radical scavenger properties of α-mangostin: thermodynamics and kinetics of HAT and RAF mechanisms. J Phys Chem B 2011; 115: 12591-12598
50 Tanaka R. Inhibitory effects of xanthone on paraquat- and NaNO₂-induced genotoxicity in cultured cells. J Toxicol Sci 2007; 32: 571-574
51 Martínez-Abundis E, García N, Correa F, Hernández-Reséndiz S, Pedraza-Chaverri J, Zazueta C. Effects of α-mangostin on mitochondrial energetic metabolism. Mitochondrion 2010; 10: 151-157
52 Jenkins RW, Canals D, Hannun YA. Roles and regulation of secretory and lysosomal acid sphingomyelinase. Cell Signal 2009; 21: 836-846
53 Corda S, Laplace C, Vicaut E, Duranteau J. Rapid reactive oxygen species production by mitochondria in endothelial cells exposed to tumor necrosis factor-α is mediated by ceramide. Am J Respir Cell Mol Biol 2001; 24: 762-768
54 Lecour S, Van Der Merwe E, Opie LH, Sack MN. Ceramide attenuates hypoxic cell death via reactive oxygen species signaling. J Cardiovasc Pharm 2006; 47: 158-163
55 Zhang DX, Zou AP, Li PL. Ceramide-induced activation of NADPH oxidase and endothelial dysfunction in small coronary arteries. Am J Physiol Heart Circ Physiol 2003; 284: H605-H612
56 Okudaira C, Ikeda Y, Kondo S, Furuya S, Hirabayashi Y, Koyano T, Saito Y, Umezawa K. Inhibition of acidic sphingomyelinase by xanthone compounds isolated from Garcinia speciosa . J Enzym Inhib Med Chem 2000; 15: 129-138
57 Yang K, Zhang KJ, Hu SY, Gu QL, Dong JB, Wang JX. Design, synthesis and biological activity of acid sphingomyelinase inhibitors. Chem J Chin Univ 2015; 36: 279-286
58 Marquez-Valadez B, Maldonado PD, Galvan-Arzate S, Mendez-Cuesta LA, Perez-De La Cruz V, Pedraza-Chaverri J, Chanez-Cardenas ME, Santamaria A. α-Mangostin induces changes in glutathione levels associated with glutathione peroxidase activity in rat brain synaptosomes. Nutr Neurosci 2012; 15: 13-19
59 Hussain SP, Harris CC. Inflammation and cancer: an ancient link with novel potentials. Int J Cancer 2007; 121: 2373-2380
60 Reuter S, Gupta SC, Chaturvedi MM, Aggarwal BB. Oxidative stress, inflammation, and cancer: how are they linked?. Free Radic Biol Med 2010; 49: 1603-1616
61 Tewtrakul S, Wattanapiromsakul C, Mahabusarakam W. Effects of compounds from Garcinia mangostana on inflammatory mediators in RAW264.7 macrophage cells. J Ethnopharmacol 2009; 121: 379-382
62 Chen LG, Yang LL, Wang CC. Anti-inflammatory activity of mangostins from Garcinia mangostana . Food Chem Toxicol 2008; 46: 688-693
63 Athar M, Back JH, Kopelovich L, Bickers DR, Kim AL. Multiple molecular targets of resveratrol: Anti-carcinogenic mechanisms. Arch Biochem Biophs 2009; 486: 95-102
64 Atluri N, Holur R, Thirumalanadhuni V, Palempalli UMD. Modulation of pro-inflammatory genes by α-mangostin from Garcinia mangostana . Int J Pharm Sci Invent 2014; 3: 23-29
65 Navya A, Nanda Kumar Y, Hari Prasad O, Santhrani T, Uma Maheswari Devi P. In vivo and in silico analysis divulges the anti-inflammatory activity of α-mangostin. Int J Appl Biotech Biochem 2012; 2: 69-80
66 Yeung F, Hoberg JE, Ramsey CS, Keller MD, Jones DR, Frye RA, Mayo MW. Modulation of NF-kappaB-dependent transcription and cell survival by the SIRT1 deacetylase. EMBO J 2004; 23: 2369-2380
67 Franceschelli S, Pesce M, Ferrone A, Patruno A, Livia P, Carlucci G, Ferrone V, Carlucci M, De Lutiis MA, Grilli A, Felaco M, Speranza L. A novel biological role of alpha-mangostin in modulating inflammatory response through the activation of SIRT-1 signaling pathway. J Cell Physiol 2016; 231: 2439-2451
68 Ramos S. Cancer chemoprevention and chemotherapy: dietary polyphenols and signalling pathways. Mol Nutr Food Res 2008; 52: 507-526
69 Lei B, Xi L, Li J, Liu H, Yao X. Global, local and novel consensus quantitative structure-activity relationship studies of 4-(phenylaminomethylene) isoquinoline-1,3(2H,4H)-diones as potent inhibitors of the cyclin-dependent kinase 4. Anal Chim Acta 2009; 644: 17-24
70 Kasala ER, Bodduluru LN, Madana RM, Athira K, Gogoi R, Barua CC. Chemopreventive and therapeutic potential of chrysin in cancer: mechanistic perspectives. Toxicol Lett 2015; 233: 214-225
71 Johnson JJ, Petiwala SM, Syed DN, Rasmussen JT, Adhami VM, Siddiqui IA, Kohl AM, Mukhtar H. α-Mangostin, a xanthone from mangosteen fruit, promotes cell cycle arrest in prostate cancer and decreases xenograft tumor growth. Carcinogenesis 2012; 33: 413-419
72 Wang JJ, Zhang W, Sanderson BJ. Altered mRNA expression related to the apoptotic effect of three xanthones on human melanoma SK-MEL-28 cell line. Biomed Res Int 2013; 2013: 715603
73 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
74 Xu Q, Ma J, Lei J, Duan W, Sheng L, Chen X, Hu A, Wang Z, Wu Z, Wu E. α-Mangostin suppresses the viability and epithelial-mesenchymal transition of pancreatic cancer cells by downregulating the PI3 K/Akt pathway. Biomed Res Int 2014; 2014: 546353
75 Itahana K, Dimri G, Campisi J. Regulation of cellular senescence by p 53. Eur J Biochem 2001; 268: 2784-2791
76 Korm S, Jeong HC, Kwon OS, Park JR, Cho H, Kim YM, Chin YW, Cha HJ. α-Mangostin induces G1 cell cycle arrest in HCT116 cells through p 38MAPK-p 16INK4 a pathway. RSC Adv 2015; 5: 34752-34760
77 Kim JH, Yoon SY, Kim CN, Joo JH, Moon SK, Choe IS, Choe YK, Kim JW. The Bmi-1 oncoprotein is overexpressed in human colorectal cancer and correlates with the reduced p 16INK4 a/p 14ARF proteins. Cancer Lett 2004; 203: 217-224
78 Ibrahim MY, Mohd Hashim N, Mohan S, Abdulla MA, Abdelwahab SI, Kamalidehghan B, Ghaderian M, Dehghan F, Ali LZ, Karimian H, Yahayu M, Ee GC, Farjam AS, Mohd Ali H. Involvement of NF-κB and HSP70 signaling pathways in the apoptosis of MDA-MB-231 cells induced by a prenylated xanthone compound, α-mangostin, from Cratoxylum arborescens . Drug Des Devel Ther 2014; 8: 2193-2211
79 Hafeez BB, Dreckschmidt NE, Colson LA, Verma AK. Dietary agent α-Mangostin inhibits growth of pancreatic cancer BxPC3 and PANC1 cells and arrests the cell cycle in G0/G1 phase: Involvement of Ras, Hedgehog, NF-κB, and STAT3 signaling networks. Cancer Res 2010; 70: Abstract 3800
80 Mizushina Y, Kuriyama I, Nakahara T, Kawashima Y, Yoshida H. Inhibitory effects of alpha-mangostin on mammalian DNA polymerase, topoisomerase, and human cancer cell proliferation. Food Chem Toxicol 2013; 59: 793-800
81 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
82 Watanapokasin R, Jarinthanan F, Jerusalmi A, Suksamrarn S, Nakamura Y, Sukseree S, Uthaisang-Tanethpongtamb W, Ratananukul P, Sano T. Potential of xanthones from tropical fruit mangosteen as anti-cancer agents: caspase-dependent apoptosis induction in vitro and in mice. Appl Biochem Biotechnol 2010; 162: 1080-1094
83 Matsumoto K, Akao Y, Kobayashi E, Ohguchi K, Ito T, Tanaka T, Iinuma M, Nozawa Y. Induction of apoptosis by xanthones from mangosteen in human leukemia cell lines. J Nat Prod 2003; 66: 1124-1127
84 Chen JJ, Long ZJ, Xu DF, Xiao RZ, Liu LL, Xu ZF, Qiu SX, Lin DJ, Liu Q. Inhibition of autophagy augments the anticancer activity of α-mangostin in chronic myeloid leukemia cells. Leuk Lymphoma 2014; 55: 628-638
85 Menasria F, Azebaze AG, Billard C, Faussat AM, Nkengfack AE, Meyer M, Kolb JP. Apoptotic effects on B-cell chronic lymphocytic leukemia (B-CLL) cells of heterocyclic compounds isolated from Guttiferaes. Leuk Res 2008; 32: 1914-1926
86 Gross A, McDonnell JM, Korsmeyer SJ. BCL-2 family members and the mitochondria in apoptosis. Genes Dev 1999; 13: 1899-1911
87 Watanapokasin R, Jarinthanan F, Nakamura Y, Sawasjirakij N, Jaratrungtawee A, Suksamrarn S. Effects of α-mangostin on apoptosis induction of human colon cancer. World J Gastroenterol 2011; 17: 2086
88 Krajarng A, Nakamura Y, Suksamrarn S, Watanapokasin R. α-Mangostin induces apoptosis in human chondrosarcoma cells through downregulation of ERK/JNK and Akt signaling pathway. J Agric Food Chem 2011; 59: 5746-5754
89 Matsumoto K, Akao Y, Yi H, Ohguchi K, Ito T, Tanaka T, Kobayashi E, Iinuma M, Nozawa Y. Preferential target is mitochondria in α-mangostin-induced apoptosis in human leukemia HL60 cells. Bioorg Med Chem 2004; 12: 5799-5806
90 Nakagawa Y, Iinuma M, Naoe T, Nozawa Y, Akao Y. Characterized mechanism of α-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: 5620-5628
91 Kaomongkolgit R, Chaisomboon N, Pavasant P. Apoptotic effect of alpha-mangostin on head and neck squamous carcinoma cells. Arch Oral Biol 2011; 56: 483-490
92 Leão M, Gomes S, Pedraza-Chaverri J, Machado N, Sousa E, Pinto M, Inga A, Pereira C, Saraiva L. Alpha-mangostin and gambogic acid as potential inhibitors of the p 53-MDM2 interaction revealed by a yeast approach. J Nat Prod 2013; 76: 774-778
93 Doi H, Shibata MA, Shibata E, Morimoto J, Akao Y, Iinuma M, Tanigawa N, Otsuki Y. Panaxanthone isolated from pericarp of Garcinia mangostana L. suppresses tumor growth and metastasis of a mouse model of mammary cancer. Anticancer Res 2009; 29: 2485-2495
94 Won YS, Lee JH, Kwon SJ, Kim JY, Park KH, Lee MK, Seo KI. α-Mangostin-induced apoptosis is mediated by estrogen receptor α in human breast cancer cells. Food Chem Toxicol 2014; 66: 158-165
95 Turcotte S, Giaccia AJ. Targeting cancer cells through autophagy for anticancer therapy. Curr Opin Cell Biol 2010; 22: 246-251
96 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: 75-80
97 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: e81572
98 Ferrara N. VEGF and the quest for tumour angiogenesis factors. Nat Rev Cancer 2002; 2: 795-803
99 Olsson AK, Dimberg A, Kreuger J, Claesson-Welsh L. VEGF receptor signalling – in control of vascular function. Nat Rev Mol Cell Biol 2006; 7: 359-371
100 Arifianti L, Rofida S, Sukardiman NCZ. Antiangiogenesis from pericarp of mangosteen on T47D breast cancer. E-Journal Planta Husada 2014; 2: 12-15
101 Lei J, Huo X, Duan W, Xu Q, Li R, Ma J, Li X, Han L, Li W, Sun H, Wu E, Ma Q. alpha-Mangostin inhibits hypoxia-driven ROS-induced PSC activation and pancreatic cancer cell invasion. Cancer Lett 2014; 347: 129-138
102 Jittiporn K, Suwanpradid J, Patel C, Rojas M, Thirawarapan S, Moongkarndi P, Suvitayavat W, Caldwell RB. Anti-angiogenic actions of the mangosteen polyphenolic xanthone derivative α-mangostin. Microvasc Res 2014; 93: 72-79
103 Shiozaki T, Fukai M, Hermawati E, Juliawaty LD, Syah YM, Hakim EH, Puthongking P, Suzuki T, Kinoshita K, Takahashi K, Koyama K. Anti-angiogenic effect of α-mangostin. J Nat Med 2013; 67: 202-206
104 Kundu JK, Surh YJ. Cancer chemopreventive and therapeutic potential of resveratrol: mechanistic perspectives. Cancer Lett 2008; 269: 243-261
105 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: 3805-3816
106 Kaomongkolgit R. Alpha-mangostin suppresses MMP-2 and MMP-9 expression in head and neck squamous carcinoma cells. Odontology 2013; 101: 227-232
107 Shih YW, Chien ST, Chen PS, Lee JH, Wu SH, Yin LT. α-Mangostin suppresses phorbol 12-myristate 13-acetate-induced MMP-2/MMP-9 expressions via αvβ3 integrin/FAK/ERK and NF-κB signaling pathway in human lung adenocarcinoma A549 cells. Cell Biochem Bioph 2010; 58: 31-44
108 Hung SH, Shen KH, Wu CH, Liu CL, Shih YW. α-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: 1291-1298
109 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. Oncology Lett 2013; 5: 1958-1964
110 Sanchez-Perez Y, Morales-Barcenas R, Garcia-Cuellar CM, Lopez-Marure R, Calderon-Oliver M, Pedraza-Chaverri J, Chirino YI. The α-mangostin prevention on cisplatin-induced apoptotic death in LLC-PK1 cells is associated to an inhibition of ROS production and p 53 induction. Chem Biol Interact 2010; 188: 144-150
111 Perez-Rojas JM, Cruz C, Garcia-Lopez P, Sanchez-Gonzalez DJ, Martinez-Martinez CM, Ceballos G, Espinosa M, Melendez-Zajgla J, Pedraza-Chaverri J. Renoprotection by α-mangostin is related to the attenuation in renal oxidative/nitrosative stress induced by cisplatin nephrotoxicity. Free Radic Res 2009; 43: 1122-1132
112 Tangpong J, Miriyala S, Noel T, Sinthupibulyakit C, Jungsuwadee P, Clair DS. Doxorubicin-induced central nervous system toxicity and protection by xanthone derivative of Garcinia mangostana . Neuroscience 2011; 175: 292-299
113 Boutros T, Chevet E, Metrakos P. Mitogen-activated protein (MAP) kinase/MAP kinase phosphatase regulation: roles in cell growth, death, and cancer. Pharmacol Rev 2008; 60: 261-310
114 Agarwal A, Das K, Lerner N, Sathe S, Cicek M, Casey G, Sizemore N. The AKT/I kappa B kinase pathway promotes angiogenic/metastatic gene expression in colorectal cancer by activating nuclear factor-kappa B and beta-catenin. Oncogene 2005; 24: 1021-1031
115 Kumazaki M, Noguchi S, Yasui Y, Iwasaki J, Shinohara H, Yamada N, Akao Y. Anti-cancer effects of naturally occurring compounds through modulation of signal transduction and miRNA expression in human colon cancer cells. J Nutr Biochem 2013; 24: 1849-1858
116 Surh YJ. Cancer chemoprevention with dietary phytochemicals. Nat Rev Cancer 2003; 3: 768-780
117 Lee YB, Ko KC, Shi MD, Liao YC, Chiang TA, Wu PF, Shih YX, Shih YW. α-Mangostin, a novel dietary xanthone, suppresses TPA-mediated MMP-2 and MMP-9 expressions through the ERK signaling pathway in MCF-7 human breast adenocarcinoma cells. J Food Sci 2010; 75: H13-H23
118 Shan T, Cui X, Li W, Lin W, Lu HW, Li Y, Chen X, Wu T. α-Mangostin suppresses human gastric adenocarcinoma cells in vitro via blockade of Stat3 signaling pathway. Acta Pharmacol Sin 2014; 35: 1065-1073
119 Ibrahim MY, Hashim NM, Mohan S, Abdulla MA, Abdelwahab SI, Arbab IA, Yahayu M, Ali LZ, Ishag OE. α-Mangostin from Cratoxylum arborescens: an in vitro and in vivo toxicological evaluation. Arabian J Chem 2015; 8: 129-137
120 Jujun P, Pootakham K, Pongpaibul Y, Duangrat C, Tharavichitkul P. Acute and repeated dose 28-day oral toxicity study of Garcinia mangostana Linn. rind extract. CMU J Nat Sci 2008; 7: 199-208
121 Bunyong R, Chaijaroenkul W, Plengsuriyakarn T, Na-Bangchang K. Antimalarial activity and toxicity of Garcinia mangostana Linn. Asian Pac J Trop Med 2014; 7: 693-698
122 Hutadilok-Towatana N, Reanmongkol W, Wattanapiromsakul C, Bunkrongcheap R. Acute and subchronic toxicity evaluation of the hydroethanolic extract of mangosteen pericarp. J Med Plant Res 2010; 4: 969-974
123 Gutierrez-Orozco F, Thomas-Ahner JM, Berman-Booty LD, Galley JD, Chitchumroonchokchai C, Mace T, Suksamrarn S, Bailey MT, Clinton SK, Lesinski GB, Failla ML. Dietary alpha-mangostin, a xanthone from mangosteen fruit, exacerbates experimental colitis and promotes dysbiosis in mice. Mol Nutr Food Res 2014; 58: 1226-1238
124 Gutierrez-Orozco F, Thomas-Ahner JM, Galley JD, Bailey MT, Clinton SK, Lesinski GB, Failla ML. Intestinal microbial dysbiosis and colonic epithelial cell hyperproliferation by dietary alpha-mangostin is independent of mouse strain. Nutrients 2015; 7: 764-784
125 Bumrungpert A, Kalpravidh RW, Suksamrarn S, Chaivisuthangkura A, Chitchumroonchokchai C, Failla ML. Bioaccessibility, biotransformation, and transport of α-mangostin from Garcinia mangostana (Mangosteen) using simulated digestion and Caco-2 human intestinal cells. Mol Nutr Food Res 2009; 53: S54-S61
126 Gutierrez-Orozco F, Chitchumroonchokchai C, Lesinski GB, Suksamrarn S, Failla ML. α-Mangostin: anti-inflammatory activity and metabolism by human cells. J Agric Food Chem 2013; 61: 3891-3900
127 Choi YH, Han SY, Kim YJ, Kim YM, Chin YW. Absorption, tissue distribution, tissue metabolism and safety of α-mangostin in mangosteen extract using mouse models. Food Chem Toxicol 2014; 66: 140-146
128 Han SY, You BH, Kim YC, Chin YW, Choi YH. Dose-independent ADME properties and tentative identification of metabolites of alpha-mangostin from Garcinia mangostana in mice by automated microsampling and UPLC-MS/MS methods. PLoS One 2015; 10: e0131587
129 Li L, Han AR, Kinghorn AD, Frye RF, Derendorf H, Butterweck V. Pharmacokinetic properties of pure xanthones in comparison to a mangosteen fruit extract in rats. Planta Med 2013; 79: 646-653
130 Tang YP, Li PG, Kondo M, Ji HP, Kou Y, Ou B. Effect of a mangosteen dietary supplement on human immune function: a randomized, double-blind, placebo-controlled trial. J Med Food 2009; 12: 755-763
131 Kondo M, Zhang L, Ji H, Kou Y, Ou B. Bioavailability and antioxidant effects of a xanthone-rich Mangosteen (Garcinia mangostana) product in humans. J Agric Food Chem 2009; 57: 8788-8792
132 Xie Z, Sintara M, Chang T, Ou B. Functional beverage of Garcinia mangostana (mangosteen) enhances plasma antioxidant capacity in healthy adults. Food Sci Nutr 2015; 3: 32-38
133 Chitchumroonchokchai C, Riedl KM, Suksumrarn S, Clinton SK, Kinghorn AD, Failla ML. Xanthones in mangosteen juice are absorbed and partially conjugated by healthy adults. J Nutr 2012; 142: 675-680
134 Xie Z, Sintara M, Chang T, Ou B. Daily consumption of a mangosteen-based drink improves in vivo antioxidant and anti-inflammatory biomarkers in healthy adults: a randomized, double-blind, placebo-controlled clinical trial. Food Sci Nutr 2015; 3: 342-348
135 Li L, Brunner I, Han AR, Hamburger M, Kinghorn AD, Frye R, Butterweck V. Pharmacokinetics of α-mangostin in rats after intravenous and oral application. Mol Nutr Food Res 2011; 55 (Suppl. 01) S67-74
136 Petiwala SM, Li G, Ramaiya A, Kumar A, Gill RK, Saksena S, Johnson JJ. Pharmacokinetic characterization of mangosteen (Garcinia mangostana) fruit extract standardized to α-mangostin in C57BL/6 mice. Nutr Res 2014; 34: 336-345
137 Fei X, Jo M, Lee B, Han SB, Lee K, Jung JK, Seo SY, Kwak YS. Synthesis of xanthone derivatives based on α-mangostin and their biological evaluation for anti-cancer agents. Bioorg Med Chem Lett 2014; 24: 2062-2065
138 Aisha AF, Ismail Z, Abu-Salah KM, Majid AM. Solid dispersions of alpha-mangostin improve its aqueous solubility through self-assembly of nanomicelles. J Pharm Sci 2012; 101: 815-825
139 Zhao Y, Tang G, Tang Q, Zhang J, Hou Y, Cai E, Liu S, Lei D, Zhang L, Wang S. A method of effectively improved alpha-mangostin bioavailability. Eur J Drug Metab Pharmacokinet 2016; 41: 605-613

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