Molecular & Cellular Toxicology

The Korean Society of Toxicogenomics and Toxicoproteomics (대한독성유전 단백체학회)
권호 표지

Amygdalin Modulates Cell Cycle Regulator Genes in Human Chronic Myeloid Leukemia Cells

  • Park, Hae-Jeong (Kohwang Medical Research Institute, Department of Pharmacology, College of Medicine, Kyung Hee University) ;
  • Baik, Haing-Woon (Department of Biochemistry and Molecular Biology, School of Medicine, Eulji University) ;
  • Lee, Seong-Kyu (Department of Biochemistry and Molecular Biology, School of Medicine, Eulji University) ;
  • Yoon, Seo-Hyun (Kohwang Medical Research Institute, Department of Pharmacology, College of Medicine, Kyung Hee University) ;
  • Zheng, Long-Tai (Kohwang Medical Research Institute, Department of Pharmacology, College of Medicine, Kyung Hee University) ;
  • Yim, Sung-Vin (Kohwang Medical Research Institute, Department of Pharmacology, College of Medicine, Kyung Hee University) ;
  • Hong, Seon-Pyo (Department of Oriental Pharmaceutical Sciences, College of Pharmacy, Kyung Hee University) ;
  • Chung, Joo-Ho (Kohwang Medical Research Institute, Department of Pharmacology, College of Medicine, Kyung Hee University)
  • Published : 2006.09.30
Download PDF
⟨ Previous Next ⟩

Abstract

To determine the anticancer effect of D-amygdalin (D-mandelinitrole-${\beta}$-D-gentiobioside) in human chronic myeloid leukemia cells K562, we profiled the gene expression between amygdalin treatment and control groups. Through 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay, the cytotoxicity of D-amygdalin was $57.79{\pm}1.83%$ at the concentration of 5 mg/mL for 24 h. We performed cDNA microarray analysis and compared the gene expression profiles between D-amygdalin (5 mg/mL, 24 h) treatment and control groups. Among the genes changed by D-amygdalin, we paid attention to cell cycle-related genes, and particularly cell cycle regulator genes; because arrest of cell cycle processing was ideal tactic in remedy for cancer. In our data, expressions of cyclin-dependent kinase inhibitor 1B (p27, Kip1) (CDKN1B), ataxia telangiectasia mutated (includes complementation groups A, C, and D) (ATM), cyclin-dependent kinase inhibitor 1C (p57, Kip2) (CDKN1C), and CHK1 checkpoint homolog (CHEK1, formally known as CHK1) were increased, while expressions of cyclin-dependent kinase 2 (CDK2), cell division cycle 25A (CDC25A), and cyclin E1 (CCNE1) were decreased. The pattern of these gene expressions were confirmed through RT-PCR. Our results showed that D-amygdalin might control cell cycle regulator genes and arrest S phase of cell cycle in K562 cells as the useful anticancer drug.

Keywords

References

  1. Sharifi, N. & Steinman, R.A. Targeted chemotherapy: chronic myelogenous leukemia as a model. J. Mol. Med. 80, 219-232 (2002) https://doi.org/10.1007/s00109-001-0305-3
  2. Goldman, J.M. & Melo, J.V. Chronic myeloid leukemia advances in biology and new approach to treatment. New Engl. J. Med. 349, 1451-1464 (2003) https://doi.org/10.1056/NEJMra020777
  3. Savage, D.G. & Antman, K.H. Imatinib mesylate?a new oral targeted therapy. N. Engl. J. Med. 346, 683- 693 (2002) https://doi.org/10.1056/NEJMra013339
  4. Koo, J.Y. et al. Quantitative determination of amygdalin epimers from armeniacae semen by liquid chromatography. J. Chromatogr. B. Analyt. Technol. Biomed. Life Sci. 814, 69-73 (2005) https://doi.org/10.1016/j.jchromb.2004.10.019
  5. Cho, C.J. et al. Hyundae-Saengyak-Hak. 8th ed. Hak- Chang Press, Seoul, pp. 470-472 (1998)
  6. Newmark, J. et al. Amygdalin (Laetrile) and prunasin beta-glucosidases: distribution in germ-free rat and in human tumor tissue. Proc. Natl. Acad. Sci. USA. 78, 6513-6516 (1981)
  7. Flora, K.P., Cradock, J.C. & Ames, M.M. A simple method for the estimation of amygdalin in the urine. Res. Commun. Chem. Pathol. Pharmacol. 20, 367- 378 (1978)
  8. Khandekar, J.D. & Edelman, H. Studies of amygdalin (laetrile) toxicity in rodents. JAMA 242, 169-171 (1979) https://doi.org/10.1001/jama.242.2.169
  9. Moertel, C.G. et al. A pharmacologic and toxicological study of amygdalin. JAMA 245, 591-594 (1998) https://doi.org/10.1001/jama.245.6.591
  10. Kwon, H.Y., Hong, S.P., Hahn, D.H. & Kim, J.H. Apoptosis induction of Persicae Semen extract in human promyelocytic leukemia (HL-60) cells. Arch. Pharm. Res. 26, 157-161 (2003) https://doi.org/10.1007/BF02976663
  11. Kawabe, T. G2 checkpoint abrogators as anticancer drugs. Mol. Cancer Ther. 3, 513-519 (2004)
  12. Wang, Z. DNA damage-induced mutagenesis: a novel target for cancer prevention. Mol. Interv. 1, 269-281 (2001)
  13. Mainprize, T.G., Taylor, M.D., Rutka, J.T. & Dirks, P.B. Cip/Kip cell-cycle inhibitors: A neuro-oncological perspective. J. Neurooncol. 51, 205-218 (2001) https://doi.org/10.1023/A:1010671908204
  14. Schwartz, G.K. & Shah, M.A. Targeting the cell cycle: a new approach to cancer therapy. J. Clin. Oncol. 23, 9408-9421 (2005) https://doi.org/10.1200/JCO.2005.01.5594
  15. Mailand, N. et al. Rapid destruction of human Cdc25A in response to DNA damage. Science 288, 1425-1429 (2000) https://doi.org/10.1126/science.288.5470.1425
  16. Mailand, N. et al. Regulation of G (2)/M events by Cdc25A through phosphorylation-dependent modulation of its stability. EMBO 21, 5911-5920 (2002) https://doi.org/10.1093/emboj/cdf567
  17. Eastman, A. Cell cycle checkpoints and their impact on anticancer therapeutic strategies. J. Cell Biochem. 91, 223-231 (2004) https://doi.org/10.1002/jcb.10699
  18. Falck, J. et al. The ATM-Chk2-Cdc25A checkpoint pathway guards against radioresistant DNA synthesis. Nature 410, 842-847 (2001) https://doi.org/10.1038/35071124
  19. Hirama, T. & Koeffler, H.P. Role of cyclin-dependent kinase inhibitors in the development of cancer. Blood 86, 841-854 (1995)
  20. Loda, M. et al. Increased proteasome-dependent degradation of the cyclin-dependent kinase inhibitor p27 in aggressive colorectal carcinomas. Nat. Med. 3, 231-234 (1997) https://doi.org/10.1038/nm0297-231
  21. Matsuoka, S. et al. p57Kip2, a structurally distinct member of the p21cip1 Cdk inhibitor family, is a candidate tumor suppressor gene. Genes Dev. 9, 650- 662 (1995) https://doi.org/10.1101/gad.9.6.650
  22. Sherr, C.J. & Roberts, J.M. CDK inhibitors: Positive and negative regulators of G1-phase progression. Genes Dev. 13, 1501-1512 (1999) https://doi.org/10.1101/gad.13.12.1501
  23. Sheaff, R.J. et al. Cyclin E-CDK2 is a regulator of p27 (Kip1). Genes Dev. 11, 1464-1478 (1997) https://doi.org/10.1101/gad.11.11.1464
  24. Lee, M.H., Reynisdottir, I. & Massague, J. Cloning of p57 (KIP2), a cyclin-dependent kinase inhibitor with unique domain structure and tissue distribution. Genes Dev. 9, 639-649 (1995) https://doi.org/10.1101/gad.9.6.639
  25. Yang, Y.H. et al. Normalization for cDNA microarray data: a robust composite method addressing single and multiple slide systematic variation. Nucleic Acids Res. 30, e15 (2002) https://doi.org/10.1093/nar/30.4.e15