Cytotoxic Activity of Mangosteen (Garcinia mangostana L.) Peel Extract and α-mangostin toward Leukemia Cell Lines (HL-60 and K-562)


Affiliations

  • School of Health Sciences Jenderal Achmad Yani, Cimahi, Indonesia
  • Aretha Medika Utama, Biomedical and Biomolecular Research Centre, Bandung, Indonesia
  • Maranatha Christian University, Faculty of Medicine, Bandung, Indonesia

Abstract

Fruit of Mangosteen (Garcinia mangostana L.) is well-known in Indonesia and other Southeast Asian countries. Studies have shown that extract of the pericarp of mangosteen contained mostly of xanthones exhibit many biological activities, especially as an antitumor. This study aimed to investigate the cytotoxic activity and selectivity of Mangosteen Peel Extract (MPE) and α-mangostin against two leukemia cell lines (HL-60 and K-562) and the normal lymphocyte cells from two different donors. The cytotoxic activity was performed using 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxyme-thoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay. Imatinib and Isotretinoin were used as a positive control to the K-562 and HL-60 cells, respectively. The MPE and α-mangostin revealed higher mortality toward leukemia cell lines rather than toward lymphocyte cells, with more than 80% of HL-60 and K-562 cells died at 6.25 and 25 μg/ml, respectively. MPE was more toxic and selective against K-562 with IC50 of 2.79 μg/ml and SI of 8.27, while α-mangostin was more toxic and selective against HL-60 with IC50 of 1.12 μg/ml and SI of 22.34. MPE and α-mangostin showed potent sensitivity and selectivity to leukemia cells, hence these are considered as promising sources for future leukemia treatment.

Keywords

Mangosteen Peel Extract, α-mangostin, acute myeloid leukemia (AML), chronic myeloid leukemia (CML), selectivity index

Subject Discipline

Pharmacy and Pharmacology

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References

Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, et al. Cancer incident and mortality worldwide: Source, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 2014; 136:349–86.

McDonald M, Hertz R, Lowcnthal SW. Pfizer facts: The burden of cancer in Asia USA: Pfizer Medical Division; 2008.

Modak H, Kulkarin SS, Kadakol GS, Hiremath SV, Patil BR, Hallikeri U, et al. Prevalence and risk of leukemia in the multi-ethnic population of North Karnataka. Asian Pac J Cancer Prev. 2011; 12:671–5.

Belson M, Kingsley B, Holmes A. Risk factors for accute leukemia in children: A review. Environ Health Persp. 2007; 115(1):138–45.

Henkes M, van der Kuip H, Aulitzky WE. Therapeutic options for chronic myeloid leukemia: focus on imatinib (Glivec®, GleevecTM). Ther Clin Risk Manag. 2008; 4(1):163–87.

Niles RM. Recent advances in the use of Vitamin A (Retinoids) in the prevention and treatment of cancer. Nutr. 2000; 16:1084–90.

Gottesman MM, Fojo T, Bates ES. Multidrug resistance in cancer. Nat Rev Cancer. 2002; 2:48–58.

Shan T, Ma Q, Guo K, Liu J, Li W, Wang F, et al. Xanthones from mangosteen extracts as natural chemopreventive agents: potential anticancer drugs. Curr Mol Med. 2011; 11(8):666–77.

Foti RS, Pearson JT, Rock DA, Wahlstrom JL, Wienkers LC. In vitro inhibition of multiple cytochrome P40 isoforms by xanthone derivatives from mangosteen extract. Drug Metab Dispos. 2009; 37(9):1848–55.

Yang J, Liu RH, Halim L. Antioxidant and antiproliferative activities of common edible nut seeds. Lwt-Food Sci Technol. 2009; 42(1):1–8.

Aisha AFA, Abu-Salah KM, Ismall Z, Abdul-Majid AMS. In vitro and in vivo anti-colon cancer effects of Garcina mangostana xanthones extract. BMC Compl Alternative Med. 2012; 12(104):1–10.

Darsono L, Hidayat M, Maesaroh M, Fauziah N, Widowati W. Ex vivo study of Garcinia mangostana L. (Mangosteen) peel extract and xanthones as anti-adipogenesis in HepG2 cell model. Int J Med Res Health Sci. 2015; 4(3):566–71.

Widowati W, Darsono L, Suherman J, Yelliantty Y, Maesaroh M. High Performance Liquid Chromatography (HPLC) analysis, antioxidant, antiaggregation of mangosteen peel extract (Garcinia mangostana L.). Int J Biosci Biochem Bioinfo. 2014; 4(6):458–66.

Boyum A. Isolation of mononuclear cells and granulocytes from human blood. Isolation of monuclear cells by one centrifugation, and of granulocytes by combining centrifugation and sedimentation at 1 g. Scand J Clin Lab Invest Suppl 1968; 97:77–89.

Mahavorasirikul W, Viyanant V, Chaijaroenkul W, Itharat A, Na-Bangchang K. Cytotoxic activity of Thai medicinal plants against human cholangiocarcinoma, laryngeal and hepatocarcinoma cells in vitro. BMC Complement Altern Med. 2010; 10(55):1–8.

Akao Y, Nakagawa Y, Iinuma M, Nozawa Y. Anti-cancer effects of xanthones from pericarps of mangosteen. Int J Mol Sci. 2008; 9:355–70.

Pedraza-Chaverri J, Cardenas-Rodriguez N, OrozcoIbarra M, Perez-Rojas JM. Medicinal properties of mangosteen (Garcinia mangostana). Food Chem Toxicol. 2008; 46:3227–39.

Hung SH, Shen KH, Wu CH, Liu CL, Shih YW. Alphamangostin 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– 8.

Chin YW, Jung HA, Chai H, Keller WJ, Kinghorn AD. Xanthones with quinone reductase-inducing activity from the fruits of Garcinia mangostana (Mangosteen). Phytochemistry. 2008; 69(3):754–8.

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; 66:1124–7.

Matsumoto K, Akao Y, Yi H, Ohguchi K, Ito T, Tanaka T, et al. Preferential target is mitochondria in alphamangostininduced apoptosis in human leukemia HL60 cells. Bioorg Med Chem. 2004; 12(22):5799–806.

Krajarng A, Nakamura Y, Suksamram S, Watanapokasin R. Preferential target is mitochondria in alpha-mangostininduced apoptosis in human leukemia HL60 cells. J Agric Food Chem. 2011; 59:5746–54.

Niles RM. Recent advances in the use of vitamin A (Retinoids) in the prevention and treatment of cancer. Nutr. 2000; 16:1084–90.

Deininger M, Buchdunger E, Druker BJ. The development of imatinib as a therapeutic agent for chronic myeloid leukemia. Blood. 2005; 105(7):2640–53.

Jacquel A, Herrant M, Legros L, Belhacene N, Luciano F, Pages G, et al. Imatinib induces mitochondria-dependent apoptosis of the Bcr-Abl-positive K562 cell line and its differentiation toward the erythroid lineage. FASEB J. 2003; 17(14):2160–2.


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