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In vivo toxicity and antitumor activity of mangosteen extract

Journal of Natural Medicines volume 67, pages 255–263 (2013)Cite this article

Abstract

Mangosteen (Garcinia mangostana) has been widely used in the traditional medicine of Thailand to treat various ailments, especially diseases of the digestive system and infections. Many reports show antiproliferation of crude extracts and active constituents from mangosteen against many cancer cell lines. Therefore, the current study is proposed to demonstrate in vivo evidence on the antitumor activity of mangosteen. Crude methanolic extract (CME) from mangosteen pericarp including 25.19 % α-mangostin as an active xanthone was used in this study. The inhibition on tumor cell proliferation of CME was preliminarily evaluated against the murine colon cancer cell line NL-17 with an IC50 value of 17 and 84 μg/ml based on WST-1 and LDH assays, respectively. The safety dose for animal application was assessed by in vivo toxicity studies using female BALB/c mice. Acute toxicity showed an LD50 value and approximate lethal dose at 1,000 mg/kg, whereas the suitable dose for short-term study should be ≤200 mg/kg. The effective dose for antitumor activity of CME was found to be between 100 and 200 mg/kg, with a tumor size reduction of 50–70 %. Histological staining clearly illustrated a decrease of tumor cell density in the footpad in a dose-dependent manner. The median survival time and life span significantly increased in tumor-bearing mice with CME treatment. This study suggests that CME possesses a powerful antitumor activity. Therefore, it is worth undertaking further investigation to identify active compounds and obtain a deeper understanding of their mechanism, in order to acquire novel effective anticancer drugs.

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References

  1. Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM (2010) Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer 127:2893–2917

    PubMed  Article  CAS  Google Scholar 

  2. Mehta RG, Pezzuto JM (2002) Discovery of cancer preventive agents from natural products: from plants to prevention. Curr Oncol Rep 4:478–486

    PubMed  Article  Google Scholar 

  3. Surh Y-J (2003) Cancer chemoprevention with dietary phytochemicals. Nat Rev Cancer 3:768–780

    PubMed  Article  CAS  Google Scholar 

  4. Luqman S, Pezzuto JM (2010) NFκB: a promising target for natural products in cancer chemoprevention. Phytother Res 24:949–963

    PubMed  CAS  Google Scholar 

  5. Wang B, Deng J, Gao Y, Zhu L, He R, Xu Y (2011) The screening toolbox of bioactive substances from natural products: a review. Fitoterapia 82:1141–1151

    PubMed  Article  CAS  Google Scholar 

  6. Farnsworth NR, Bunyapraphatsara N (1992) Thai medicinal plants recommended for primary health care system. Mahidol University, Bangkok

    Google Scholar 

  7. Suksamrarn S, Suwannapoch N, Phakhodee W, Thanuhiranlert J, Ratananukul P, Chimnoi N, Suksamrarn A (2003) Antimycobacterial activity of prenylated xanthones from the fruits of Garcinia mangostana. Chem Pharm Bull (Tokyo) 51:857–859

    Article  CAS  Google Scholar 

  8. Pedraza-Chaverri J, Cárdenas-Rodríguez N, Orozco-Ibarra M, Pérez-Rojas JM (2008) Medicinal properties of mangosteen (Garcinia mangostana). Food Chem Toxicol 46:3227–3239

    PubMed  Article  CAS  Google Scholar 

  9. Chairungsrilerd N, Furukawa K, Ohta T, Nozoe S, Ohizumi Y (1996) Pharmacological properties of alpha-mangostin, a novel histamine H1 receptor antagonist. Eur J Pharmacol 314:351–356

    PubMed  Article  CAS  Google Scholar 

  10. Gopalakrishnan G, Banumathi B, Suresh G (1997) Evaluation of antifungal activity of natural xanthones from Garcinia mangostana and their synthetic derivatives. J Nat Prod 60:519–524

    PubMed  Article  CAS  Google Scholar 

  11. Iinuma M, Tosa H, Tanaka T, Asai F, Kobayashi Y, Shimano R, Miyauchi K (1996) Antibacterial activity of xanthones from guttiferaeous plants against methicillin-resistant Staphylococcus aureus. J Pharm Pharmacol 48:861–865

    PubMed  Article  CAS  Google Scholar 

  12. Pothitirat W, Chomnawang MT, Supabphol R, Gritsanapan W (2010) Free radical scavenging and anti-acne activities of mangosteen fruit rind extracts prepared by different extraction methods. Pharm Biol 48:182–186

    PubMed  Article  CAS  Google Scholar 

  13. Chen SX, Wan M, Loh BN (1996) Active constituents against HIV-1 protease from Garcinia mangostana. Planta Med 62:381–382

    PubMed  Article  CAS  Google Scholar 

  14. Fan C, Su J (1997) Antioxidative mechanism of isolated components from methanol extract of fruit hulls of Garcinia mangostana L. J Chin Agric Chem Soc 35:540–551

    CAS  Google Scholar 

  15. Kosem N, Han Y-H, Moongkarndi P (2007) Antioxidant and cytoprotective activities of methanolic extract from Garcinia mangostana hulls. ScienceAsia 33:283–292

    Article  CAS  Google Scholar 

  16. Jung HA, Su BN, Keller WJ, Mehta RG, Kinghorn AD (2006) Antioxidant xanthones from the pericarp of Garcinia mangostana (Mangosteen). J Agric Food Chem 54:2077–2082

    PubMed  Article  CAS  Google Scholar 

  17. Weecharangsan W, Opanasopit P, Sukma M, Ngawhirunpat T, Sotanaphun U, Siripong P (2006) Antioxidative and neuroprotective activities of extracts from the fruit hull of mangosteen (Garcinia mangostana Linn.). Med Princ Pract 15:281–287

    PubMed  Article  Google Scholar 

  18. Moongkarndi P, Srisawat C, Saetun P, Jantaravinid J, Peerapittayamongkol C, Soi-ampornkul R, Junnu S, Sinchaikul S, Chen ST, Charoensilp P, Thongboonkerd V, Neungton N (2010) Protective effect of mangosteen extract against β-amyloid-induced cytotoxicity, oxidative stress and altered proteome in SK-N-SH cells. J Proteome Res 9:2076–2086

    PubMed  Article  CAS  Google Scholar 

  19. Moongkarndi P, Kosem N, Kaslungka S, Luanratana O, Pongpan N, Neungton N (2004) Antiproliferation, antioxidation and induction of apoptosis by Garcinia mangostana (mangosteen) on SKBR3 human breast cancer cell line. J Ethnopharmacol 90:161–166

    PubMed  Article  Google Scholar 

  20. Ho CK, Huang YL, Chen CC (2002) Garcinone E, a xanthone derivative, has potent cytotoxic effect against hepatocellular carcinoma cell lines. Planta Med 68:975–979

    PubMed  Article  CAS  Google Scholar 

  21. Matsumoto K, Akao Y, Kobayashi E, Ohguchi K, Ito T, Tanaka T, Iinuma M, Nozawa Y (2003) Induction of apoptosis by xanthones from mangosteen in human leukemia cell lines. J Nat Prod 66:1124–1127

    PubMed  Article  CAS  Google Scholar 

  22. Akao Y, Nakagawa Y, Iinuma M, Nozawa Y (2008) Anti-cancer effects of xanthones from pericarps of mangosteen. Int J Mol Sci 9:355–370

    PubMed  Article  CAS  Google Scholar 

  23. Watanapokasin R, Jarinthanan F, Jerusalmi A, Suksamrarn S, Nakamura Y, Sukseree S, Uthaisang-Tanethpongtamb W, Ratananukul P, Sano T (2010) Potential of xanthones from tropical fruit mangosteen as anti-cancer agents: caspase-dependent apoptosis induction in vitro and in mice. Appl Biochem Biotechnol 162:1080–1094

    PubMed  Article  CAS  Google Scholar 

  24. Khonkarn R, Okonogi S, Ampasavate C, Anuchapreeda S (2010) Investigation of fruit peel extracts as sources for compounds with antioxidant and antiproliferative activities against human cell lines. Food Chem Toxicol 48:2122–2129

    PubMed  Article  CAS  Google Scholar 

  25. Tsuruo T, Yamori T, Naganuma K, Tsukagoshi S, Sakurai Y (1983) Characterization of metastatic clones derived from a metastatic variant of mouse colon adenocarcinoma 26. Cancer Res 43:5437–5442

    PubMed  CAS  Google Scholar 

  26. Takenouchi T, Munekata E (1995) Trophic effects of substance P and β-amyloid peptide on dibutyryl cyclic AMP-differentiated human leukemic (HL-60) cells. Life Sci 56:PL479–PL484

    PubMed  Article  CAS  Google Scholar 

  27. Decker T, Lohmann-Matthes ML (1988) A quick and simple method for the quantitation of lactate dehydrogenase release in measurements of cellular cytotoxicity and tumor necrosis factor (TNF) activity. J Immunol Methods 115:61–69

    PubMed  Article  CAS  Google Scholar 

  28. World Health Organization (WHO) (2000) General guidelines for methodologies on research and evaluation of traditional medicine. WHO, Geneva

    Google Scholar 

  29. Gupta M, Mazumder UK, Rath N, Mukhopadhyay DK (2000) Antitumor activity of methanolic extract of Cassia fistula L. seed against Ehrlich ascites carcinoma. J Ethnopharmacol 72:151–156

    PubMed  Article  CAS  Google Scholar 

  30. Holland EC (2004) Mouse models of human cancer. Wiley-Liss, New York

    Book  Google Scholar 

  31. Schmid W (1855) Ueber das mangostin. Liebigs Ann Chem 93:83–89

    Article  Google Scholar 

  32. Matsumoto K, Akao Y, Yi H, Ohguchi K, Ito T, Tanaka T, Kobayashi E, Iinuma M, Nozawa Y (2004) Preferential target is mitochondria in α-mangostin-induced apoptosis in human leukemia HL60 cells. Bioorg Med Chem 12:5799–5806

    PubMed  Article  CAS  Google Scholar 

  33. Jujun P, Pootakham K, Pongpaibul Y, Duangrat C, Tharavichitkul P (2008) Acute and repeated dose 28-day oral toxicity study of Garcinia mangostana Linn. rind extract. CMU J Nat Sci 7:199–208

    Google Scholar 

  34. Sornprasit A, Sripiyarattanakul K, Chuay-Yim P, Tanakittiham P (1987) Preliminary toxicological study of mangostin. Songklanakarin J Sci Technol 9:51–57

    CAS  Google Scholar 

  35. Hutadilok-Towatana N, Reanmongkol W, Wattanapiromsakul C, Bunkrongcheap R (2010) Acute and subchronic toxicity evaluation of the hydroethanolic extract of mangosteen pericarp. J Med Plant Res 4:969–974

    Google Scholar 

  36. Doi H, Shibata MA, Shibata E, Morimoto J, Akao Y, Iinuma M, Tanigawa N, Otsuki Y (2009) Panaxanthone isolated from pericarp of Garcinia mangostana L. suppresses tumor growth and metastasis of a mouse model of mammary cancer. Anticancer Res 29:2485–2495

    PubMed  CAS  Google Scholar 

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Acknowledgments

The authors would like to thank the Thailand Research Fund through the Royal Golden Jubilee Ph.D. Program (Grant No. PHD/0011/2547), Medical Plant Research Institute, Ministry of Public Health, and Faculty of Pharmacy, Mahidol University, for the financial support.

Conflict of interest

The authors declare that there are no conflicts of interest.

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Affiliations

  1. Innovation Center for Medical Redox Navigation, Kyushu University, Fukuoka, 812-8582, Japan

    Nuttavut Kosem, Kazuhiro Ichikawa & Hideo Utsumi

  2. Department of Microbiology, Faculty of Pharmacy, Mahidol University, Bangkok, 10400, Thailand

    Primchanien Moongkarndi

Authors
  1. Nuttavut Kosem
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  2. Kazuhiro Ichikawa
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  3. Hideo Utsumi
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  4. Primchanien Moongkarndi
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Correspondence to Primchanien Moongkarndi.

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Kosem, N., Ichikawa, K., Utsumi, H. et al. In vivo toxicity and antitumor activity of mangosteen extract. J Nat Med 67, 255–263 (2013). https://doi.org/10.1007/s11418-012-0673-8

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  • DOI: https://doi.org/10.1007/s11418-012-0673-8

Keywords

  • Garcinia mangostana
  • α-Mangostin
  • Antiproliferative activity
  • In vivo toxicity
  • Antitumor activity