Cytotoxic Effect of Fruit of Prunus mandshurica on Human Monocytic Leukemia Cells

  • Chung, Ha-Sook (Department of Food and Nutrition, College of Natural Sciences, Duksung Women′s University)
  • 발행 : 2004.09.01


Prunus mandshurica var. glabra Nakai (Rosaceae) is widely distributed in South Korea and bears a fruit with a bitter and astringent taste. An ethyl acetate-soluble extract of Prunus mandshurica was found to exhibit significant cytotoxicity against human leukemia cell lines. Bioassay-directed fractionation of this extract using an MTT(3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) cell proliferation assay as a monitor led to the isolation of the bioactive compounds. Two compounds, 1 and 2 were subsequently found to mediate cytotoxicity against U937, human monocytic leukemia cells. The 50% growth inhibitory concentrations ($IC_{50}$/) of compounds 1 and 2 on U937 were 40 and 62 $\mu\textrm{g}$/mL, respectively.


  1. Kinghorn AD, Balandrin MF. 1993. In Human Medicinal Agents from Plants. ACS Symposium Series No. 534, American Chemical Society, Washington, DC
  2. Jung HA, Jung MJ, Kim JY, Chung HY, Choi JS. 2003. Inhibitory activity of flavonoids from Prunus davidiana and other flavonoids on total ROS and hydroxyl radical generation. Arch Pharm Res 26: 809-815
  3. Olszewska M, Wolbis M. 2002. Further flavonoids from the flowers of Prunus spinosa L. Acta Pol Pharm 59: 133-137
  4. Sang S, Lapsley K, Jeong WS, Lachance PA, Ho CT, Rosen RT. 2002. Antioxidative phenolic compounds isolated from almond skins (Prunus amygdalus Batsch). J Agric Food Chem 50: 2459-2463
  5. Kikuzaki H, Kayano S, Fukutsuka N, Aoki A, Kasamatsu K, Yamasaki Y, Mitani T, Nakatani N. 2004. Abscisic acid related compounds and lignans in prunes (Prunus domestica L.) and their oxygen radical absorbance capacity (ORAC). J Agric Food Chem 52: 344-349
  6. Jung HA, Chung HY, Jung JH, Choi JS. 2004. A new pentacyclic triterpenoid glucoside from Prunus serrulata var. spontanea. Chem Pharm Bull (Tokyo) 52: 157-159
  7. Fukuda T, Ito H, Mukainaka T, Tokuda H, Nishino H, Yoshida T. 2003. Anti-tumor promoting effect of glycosides from Prunus persica seeds. Biol Pharm Bull 26: 271-273
  8. Yang YM, Hyun JW, Sung MS, Chung HS, Kim BK, Paik WH, Kang SS, Park JG. 1996. The cytotoxicity of psoralidin from Psoralea corylifolia. Planta Med 62: 353-354
  9. Hyun JW, Yang YM, Sung MS, Chung HS, Paik WH, Kang SS, Park JG. 1996. The cytotoxic activity of sterol derivatives from Pulsatilla chinensis Regal. J Kor Cancer Assoc 28: 145-150
  10. Chung HS. 1999. Cytotoxicity from some Korean edible plants. Kor J Soc Food Sci 15: 108-113
  11. Chung HS. 2001. Guaianolide sesquiterpene lactone from Ixeris sonchifolia hance with cytotoxicity in cultured human stomach and colon cancer cell lines. Food Sci Biotechnol 10: 433-436
  12. Chung HS, Hyun JW. 2004. Cyanidin and malvidin from Oryza sativa cv. Heugjinjubyeo mediates cytotoxicity against human monocytic leukemia cells by arrest of G2/M phase and induction of apoptosis. J Agric Food Chem 52: 2213-2217
  13. Carmichael J, DeGraff WG, Gazdar AF, Minna JD. Mitchell JB. 1987. Evaluation of a tetrazolium-based semiautomated colorimetric assay: assessment of chemosensitivity testing. Cancer Res 47: 936-942
  14. Liu Y, Peterson DA, Kimura H, Schubert D. 1997. Mechanism of cellular 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reduction. J Neurochem 69: 581-593
  15. Markham KR, Mabry TJ. 1975. Ultraviolet-visible and proton magnetic resonance spectroscopy of flavonoids. In The Flavonoids. Harborne JB, Mabry TJ, Mabry H, eds. Chapman and Hall, London. p 45-126
  16. Agrawal PK, Thakur RS, Bansal MC. 1989. Flavonoids. Agrawal PK, ed. Elsevier, Amsterdam. p 95-168
  17. Lee LT, Huang YT, Hwang JJ, Lee AY, Ke FC, Huang CJ, Kandaswami C, Lee PP, Lee MT. 2004. Transinactivation of the epidermal growth factor receptor tyrosine kinase and focal adhesion kinase phosphorylation by dietary flavonoids: effect on invasive potential of human carcinoma cells. Biochem Pharmacol 67: 2103-2114
  18. Tsuruga M, Dang Y, Shiono Y, Oka S, Yamazaki Y. 2003. Differential effects of vitamin E and three hydrophilic antioxidants on the actinomycin D-induced and colcemid- accelerated apoptosis in human leukemia CMK-7 cell line. Mol Cell Biochem 250: 131-137
  19. Yoshimizu N, Otani Y, Saikawa Y, Kubota T, Yoshida M, Furukawa T, Kumai K, Kameyama K, Fujii M, Yano M, Sato T, Ito A, Kitajima M. 2004. Anti-tumour effects of nobiletin, a citrus flavonoid, on gastric cancer include: antiproliferative effects, induction of apoptosis and cell cycle deregulation. Aliment Pharmacol Ther 1: 95-101
  20. Chu SC, Chiou HL, Chen PN, Yang SF, Hsieh YS. 2004. Silibinin inhibits the invasion of human lung cancer cells via decreased productions of urokinase-plasminogen activator and matrix metalloproteinase-2. Mol Carcinog 40: 143-149
  21. Heo HJ, Kim DO, Choi SJ, Shin DH, Lee CY. 2004. Potent inhibitory effect of flavonoids in Scutellaria baicalensis on amyloid beta protein-induced neurotoxicity. J Agric Food Chem 52: 4128-4132
  22. Imai Y, Tsukahara S, Asada S, Sugimoto Y. 2004. Phytoestrogens/flavonoids reverse breast cancer resistance protein/ABCG2-mediated multidrug resistance. Cancer Res 64: 4346-4352
  23. Di Virgilio AL, Iwami K, Watjen W, Kahl R, Degen GH. 2004. Genotoxicity of the isoflavones genistein, daidzein and equol in V79 cells. Toxicol Lett 151: 151-162
  24. Fujimoto K, Hosotani R, Doi R, Wada M, Lee JU, Koshiba T, Miyamoto Y, Tsuji S, Nakajima S, Imamura M. 1999. Induction of cell-cycle arrest and apoptosis by a novel retinobenzoic-acid derivative, TAC-101, in human pancreatic-cancer cells. Int J Cancer 81: 637-644<637::AID-IJC21>3.0.CO;2-4
  25. Johnson PA, Clements P, Hudson K, Caldecott KW. 1999. A mitotic spindle requirement for DNA damage-induced apoptosis in Chinese hamster ovary cells. Cancer Res 59: 2696-2700
  26. Orren DK, Petersen LN, Bohr VA. 1997. Persistent DNA damage inhibits S-phase and G2 progression, and results in apoptosis. Mol Biol Cell 8: 1129-1142
  27. Choi EJ, Lee BH. 2004. Evidence for genistein mediated cytotoxicity and apoptosis in rat brain. Life Sci 75: 499- 509
  28. Lee R, Kim YJ, Lee YJ, Chung HW. 2004 The selective effect of genistein on the toxicity of bleomycin in normal lymphocytes and HL-60 cells. Toxicology 195: 87-95
  29. Su SJ, Chow NH, Kung ML, Hung TC, Chang KL. 2003. Effects of soy isoflavones on apoptosis induction and G2- M arrest in human hepatoma cells involvement of caspase- 3 activation, Bcl-2 and Bcl-XL downregulation, and Cdc2 kinase activity. Nutr Cancer 45: 113-123
  30. Song EK, Kim JH, Kim JS, Cho H, Nan JX, Sohn DH, Ko GI, Oh H, Kim YC. 2003. Hepatoprotective phenolic constituents of Rhodiola sachalinensis on tacrine-induced cytotoxicity in Hep G2 cells. Phytother Res 17: 563- 565
  31. Nakayama T, Yamada M, Osawa T, Kawakishi S. 1993. Suppression of active oxygen-induced cytotoxicity by flavonoids. Biochem Pharmacol 45: 265-267
  32. Hirano T, Gotoh M, Oka K. 1994. Natural flavonoids and lignans are potent cytostatic agents against human leukemic HL-60 cells. Life Sci 55: 1061-1069
  33. Pagliacci MC, Spinozzi F, Migliorati G, Fumi G, Smacchia M, Grignani F, Riccardi C, Nicoletti I. 1993. Genistein inhibits tumour cell growth in vitro but enhances mitochondrial reduction of tetrazolium salts: a further pitfall in the use of the MTT assay for evaluating cell growth and survival. Eur J Cancer 29: 1502-1503
  34. den Boer ML, Pieters R, Kazemier KM, Janka-Schaub GE, Henze G, Veerman AJ. 1998. The modulating effect of PSC 833, cyclosporin A, verapamil and genistein on in vitro cytotoxicity and intracellular content of daunorubicin in childhood acute lymphoblastic leukemia. Leukemia 12: 912-920