Apoptosis Induction of Persicae Semen Extract in Human Promyelocytic Leukemia (HL-60) Cells

  • Kwon, Hee-Young (Department of Biochemistry, College of Dentistry, Kyung Hee University) ;
  • Hong, Seon-Pyo (Department of Oriental Pharmaceutical Sciences, Kyung Hee University) ;
  • Hahn, Dong-Hoon (Department of Oriental Pharmaceutical Sciences, Kyung Hee University) ;
  • Kim, Jeong-Hee (Department of Oriental Pharmaceutical Sciences, Kyung Hee University)
  • Published : 2003.02.01

Abstract

The major ingredient of Persicae Semen is a cynogenic compound, amygdalin (D-mandelonitrile-$\beta$-gentiobioside). Controversial results on the anticancer activity of amygdalin were reported due to its conversion to its inactive isomer, neoamygdalin. In order to inhibit the epimerization of amygdalin, we used newly developed simple acid boiling method in preparation of Persicae Semen extract. HPLC analysis revealed most of amygdalin in Persicae Semen extract was active D-form. Persicae Semen extract was used to analyze its effect on cell proliferation and induction of apoptosis in human promyelocytic leukemia (HL-60) cells. Persicae Semen extract was cytotoxic to HL-60 cells with $IC_{50}$ of 6.4 mg/mL in the presence of 250 nM of $\beta$-glucosidase. The antiproliferative effects of Persicae Semen extract appear to be attributable to its induction of apoptotic cell death, as Persicae Semen extract induced nuclear morphology changes and internucleosomal DNA fragmentation.

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References

  1. Bertrand, R. and San$\dot{e}$, A. T., Caspase inhibition in camptothecintreated U-937 is coupled with a shift from apoptosis to transient G1 arrest followed by necrotic cell death. Cancer Res., 59, 3565-3569 (1999)
  2. Brimer, L., Cicalini, A. R., Federici, F., Nout, R. M., Petruccioli, M., and Pulci, V., Two-step hydrolysis of amygdalin in molds. Riv. Biol., 89, 493-496 (1996)
  3. Dicenta, F., Martinez-Gomez, P., Grane, N., Martin, M. L., Leon, A., Canovas, J. A., and Berenguer, V., Relationship between cyanogenic compounds in kernels, leave and roots of sweet and bitter kernelled almonds. J. Agric. Food Chem., 50, 2149-2152 (2002) https://doi.org/10.1021/jf0113070
  4. Hyun, S. J., Yoon, M. Y., Kim, T. H., Kim, and J. H., Enhancement of mitogen-stimulated proliferation of low dose radiationadapted mouse splenocytes. Anticancer Res., 17, 225-229 (1997)
  5. Hwang, E. Y., Lee, J. H., Lee, Y. M., and Hong, S. P., Reversephase HPLC separation of D-amygdalin and neoamygdalin optimum conditions for inhibition of racemization of amygdalin. Chem. Pharm. Bull., 50, 1373-1375 (2002) https://doi.org/10.1248/cpb.50.1373
  6. Isozaki, T, Matano, Y., Yamamoto, K., and Kosaka, N., Quantitive determination of amygdain cpimers by cyclodextrin-modified micellar electrokinetic chromatography. J. Chrommatography A., 923, 249-254 (2001) https://doi.org/10.1016/S0021-9673(01)00969-4
  7. Kang, S. H., Jung, H., Kim, N., Shin, D. H., and Chung, D. S., Micellar electrokinetic chromatography for the analysis of Damygdalin its epimer in apricot kernel. J. Chromatogr A., 866, 253-259 (2000) https://doi.org/10.1016/S0021-9673(99)01107-3
  8. Kerr, J. F., Winterford, C. M., and Harmon, B. V., Apoptosis: Its significance in cancer and cancer therapy. Cancer, 73, 2013-2026 (1994) https://doi.org/10.1002/1097-0142(19940415)73:8<2013::AID-CNCR2820730802>3.0.CO;2-J
  9. Koeffler, H. P., Lowe, L., and Golde, D. W., Amygdalin (Laetrile): Effect on clonogenic cells from human myeloid leukemia cell lines and normal human marrow. Cancer Treat. Rep., 64, 105-109 (1980)
  10. Lee, S. J., Ko, W. G., Kim, J. H., Sung, G. H., Lee, S. J., Moon, C. K., and Lee, B. H., Induction of apoptosis by a novel intestinal metabolite of Ginseng Saponin via cytochrome c-mediated activation of Caspase-3 protease. Biochem. Pharm, 60, 667-685 (2000)
  11. Lilenbaum, R. C. and Green, M. R., Novel chemotherapeutic agents in the treatment of non-small-cell lung cancer. J. Clin. Onco., 11, 1391-1402 (1993) https://doi.org/10.1200/JCO.1993.11.7.1391
  12. Lim, T. H., Leem, M. J., Shin, D. H., Chang, H. B., Hong, S. W., Moon, E. Y., Lee, D. K., Yoon, S. J., and Woo, W. S., Cytotoxic constituents from the roots of Anthriscus sylvestris. Arch. Pharm. Res., 22, 208-212 (1999) https://doi.org/10.1007/BF02976548
  13. Llorens, O., Filizola, M., Spisani, S., Marastoni, M., Herranz, C., and Perez, J. J., Amygdain binds to the CD4 receptor as suggested from molecular modeling studies. Bioorg. Med. Chem. Lett., 8, 781-786 (1998) https://doi.org/10.1016/S0960-894X(98)00120-6
  14. Moertel, C. G., Fleming, T. R., Rubin, J., Kvols, L. K., Sarna, G., Koch, R., Currie, V. E., Yo, C. W., Jones, S. E., and Davignon, J. P., N. Engl. Med., 306, 201-206 (1982) https://doi.org/10.1056/NEJM198201283060403
  15. Monks, A., Scudiero, D., Skehan, P., Shoemaker, R., Paull, K., Vistica, D., Hose, C., Langley, J., Cronise, P., Vaigro-Wolff, A., Gray-Goodrich, M., Campbell, H., Mayo, J., and Boyd, M., Feasibility of a high-flux anticancer drug screening using a diverse panel of human tumor cell lines. J. Natl. Cancer Inst., 83, 757-766 (1991) https://doi.org/10.1093/jnci/83.11.757
  16. Newmark, J., Brady, R. O., Grimley, P. M., Gal, A. E., Waller, S. G., and Thistlethwaite, J. R., Amygdalin (Laetrile) and prunasin beta-glucosidases: Distribute in germ free rat and human tumor tissue. Proc. Natl. Acad. Sci. USA, 78, 6513-6516 (1981) https://doi.org/10.1073/pnas.78.10.6513
  17. Pezzuto, J. M., Plant-derived anticancer agents. Biochem Pharm., 53, 121-133 (1997) https://doi.org/10.1016/S0006-2952(96)00654-5
  18. Strugala, G. J., Stahl, R., Elsenhans, B., Rauws, A. G., and Forth, W., Small-intestinal transfer mechanism of prunasin, the primary metabolite of the cyanogenic glycoside amygdain. Hum Exp Toxicol, 14, 895-901 (1995) https://doi.org/10.1177/096032719501401107
  19. Syrigcs, K. N., Rowlinson-Busza, G., and Epenetos, A. A., In vitro cytotoxicity following specific activation of amygdain beta-glucosidase conjugated to a bladder cancer-associated monoclonal antibody. lnt. J. Cancer, 78, 712-179 (1998) https://doi.org/10.1002/(SICI)1097-0215(19981209)78:6<712::AID-IJC8>3.0.CO;2-D
  20. Takayama, Y. and Kawai, S., Study on the prevention of racemization of amygdain. Chem. Pharm. Bull., 32, 772-781 (1984)
  21. Yuan, D., Komatsu, K., Cui, Z., and Kano, Y., Pharmacological properties of traditional medicines. XXV. Effect of ephedrine, amygdalin, glycyrrhizin, gypsum and their combinations on body temperature and body fluid. Biol. Pharm. Bull., 22, 165-171 (1999) https://doi.org/10.1248/bpb.22.165