Garcinone E, a Xanthone Derivative, has Potent Cytotoxic Effect Against Hepatocellular Carcinoma Cell Lines

Abstract

Treatment of hepatocellular carcinomas (HCCs) with chemotherapy has generally been disappointing and it is most desirable to have more effective new drugs. We extracted and purified 6 xanthone compounds from the rinds (peel) of the fruits of Garcinia mangostana L., using partitioned chromatography and then tested the cytotoxic effects of these compounds on a panel of 14 different human cancer cell lines including 6 hepatoma cell lines, based on the MTT method. Several commonly used chemotherapeutic agents were included in the assay to determine the relative potency of the potential new drugs. Our results have shown that one of the xanthone derivatives which could be identified as garcinone E has potent cytotoxic effect on all HCC cell lines as well as on the other gastric and lung cancer cell lines included in the screen. We suggest that garcinone E may be potentially useful for the treatment of certain types of cancer.

Key words

Garcinone E - xanthones - hepatocellular carcinoma - chemotherapy - Garcinia mangostana - Guttiferae

References

• 1 Govindachari T R, Kalyanaraman P S, Muthukumaraswamy N. Xanthones of Garcinia mangostana Linn.  Tetrahedron. 1971;  27 3919-26
• 2 Goncalves D E, Oliverira W, Gottlieb O R, Lins Mesquita A A. Xanthones from Tovomita macrophylla .  Phytochemistry. 1972;  11 3323-5
• 3 Chanarat P, Chanarat N, Fujihara M, Nagumo T. Immunopharmacological activity of polysaccharide from the pericarb of mangosteen garcinia: phagocytic intracellular killing activities.  J Med Asso Thail. 1997;  80 S149-54
• 4 Gopalakrishnan C, Shankaranarayanan D, Kameswaran L, Nazimudeen S K. Effect of mangostin, a xanthone from Garcinia mangostana Linn. in immunopathological & Inflammatory reactions.  Indian J Exper Biol. 1980;  18 843-6
• 5 Iinuma M, Tosa H, Tanaka T, Asai F, Kobsyashi Y, Shimano R, Miyauchi K I. Antibacterial activity of xanthones from Guttiferaeous plants against methicillin-resistant Staphylococcus aureus .  J Pharm Pharmacol. 1996;  48 861-5
• 6 Shankaranarayan D, Gopalakrishnan C, Kameswaran L. Pharmacological profile of mangostin and its derivatives.  Arch Internat Pharmaco Therapie. 1979;  239 257-69
• 7 Edenharder R, Tang X. Inhibition of the mutagenicity of 2-nitrofluorene, 3-nitrofluranthene and 1-nitropyrene by flavonoids, coumarians, quinones and other phenolic compounds.  Food and Chem Toxicol. 1997;  35 357-72
• 8 Liou S S, Sheih W L, Cheng T H, Won S J, Lin C N. γ-Pyrone compounds as potential anti-cancer drugs.  J Pharm Pharmaco . 1993;  45 791-4
• 9 Lin C N, Liou S J, Lee T H, Chuang Y C, Won S J. Xanthone derivatives as potential anti-cancer drugs.  J Pharm Pharmacol. 1996;  48 539-44
• 10 Lin J H, Tong M J, Stevenson D. A new human hepatocellular carcinoma cell line secreting hepatitis B surface antigen and alpha-fetoprotein. In: GN Vyas, JL Dienstag, JH Hoofragle (eds) Viral hepatitis and liver disease. Orlando; Grune & Atralton (abstr) 1984,: p. 67
• 11 Chang C, Lin O, Lee T W, Chou C K, Lee T S, Liu T J, P'eng F K, Chen T Y, Hu C P. Induction of plasma protein secretion in a newly established human hepatoma cell line.  Mol Cell Biol. 1983;  2 1133-9
• 12 Taki T, Ishikawa H, Imai K, Yachi A, Matsumoto M. Immunological analysis of glycolipids on cell surfaces of cultured human tumor cell lines: Expression of lactoneotetrasylcaramide on tumor cell surfaces.  J Biochem. 1985;  98 887-95
• 13 Baba M, Hasegawa H, Nakayaba M, Shimiza N, Suzuki S, Kamada N, Tani K. Establishment and characterization of a gastric cancer cell line (HUGC-00HIRA) producing high levels of G-CSF, GM-CSF and IL-6: The presence of autocrine growth control by G-CSF.  Am J Hematol. 1995;  49 207-15
• 14 Huang Y L, Chen C C, Chen Y J, Huang R L, Shieh B J. Three Xanthones and Benzophenone from Garcinia mangostana .  J Nat Prod. 2001;  64 903-6
• 15 Mosmann T. A rapid colorimetric assay for cellular growth and cytotoxicity assays.  J Immunol Methods. 1983;  65 55-63
• 16 Majumder P L, Sen R C. Moscatilin, a bibenzyl derivative from the orchid Dendrobium moscatum .  Phytochemistry. 1987;  26 2121-5
• 17 Sakai S I, Katsura M, Takayama H, Aimi N, Chokethaworn N, Surttajit M. The structure of garcinone.  Chem Pharm Bull. 1993;  41 958-60
• 18 Okuda K, Obata H, Nakajima Y, Ohtsuki T, Okazaki N, Ohnishi K. Prognosis of primary hepatocellular carcinoma.  Hepatology. 1984;  4 3S-6S
• 19 Carr B I. Escalating cisplatin doses by hepatic artery infusion (HAI) for advanced stage hepatocellular carcinoma (HCC). Carr BI Sixth International Congress on anti-cancer treatment 1996,: p. 367
• 20 Nerenstone S R, Ihde D C, Friedman M A. Clinical trials in primary hepatocellular carcinoma: current status and future directions.  Cancer Treat Rev. 1988;  15 1-31
• 21 Lee Y -TN. Systemic and regional treatment of primary carcinoma of the liver.  Cancer Treat Rev. 1977;  4 195-212