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Cooperative Induction of HL-60 Cell Differentiation by Combined Treatment with Eugenol and 1α,25-Dihydroxyvitamin D3

Eugenol과 1α,25-dihydroxyvitamin D3의 병합처리에 의한 HL-60 세포의 분화 유도

  • Oh, Mi-Kyung (Department of Natural Sciences, College of Medicine, The Catholic University of Korea) ;
  • Park, Seon-Joo (Department of Natural Sciences, College of Medicine, The Catholic University of Korea) ;
  • Kim, Nam-Hoon (Department of Natural Sciences, College of Medicine, The Catholic University of Korea) ;
  • Cho, Jin-Kyung (Department of Natural Sciences, College of Medicine, The Catholic University of Korea) ;
  • Jin, Jong-Youl (Department of Internal Medicine, College of Medicine, The Catholic University of Korea) ;
  • Kim, In-Sook (Department of Natural Sciences, College of Medicine, The Catholic University of Korea)
  • 오미경 (가톨릭대학교 의과대학 자연과학교실) ;
  • 박선주 (가톨릭대학교 의과대학 자연과학교실) ;
  • 김남훈 (가톨릭대학교 의과대학 자연과학교실) ;
  • 조진경 (가톨릭대학교 의과대학 자연과학교실) ;
  • 진종률 (가톨릭대학교 의과대학 내과) ;
  • 김인숙 (가톨릭대학교 의과대학 자연과학교실)
  • Published : 2007.09.30

Abstract

Eugenol (4-allyl-2-methoxyphenol) is a main component of essential oils obtained from various spices. Recent reports have shown that eugenol induces growth inhibition and apoptosis of malignant tumor cells. In this study, the stimulatory effect of eugenol on cell differentiation was investigated in HL-60 promyelocytic leukemia cells. When HL-60 cells were treated in combination with 150 ${\mu}M$ of eugenol and 3 nM of $1{\alpha},25-dihydroxyvitamin$ $D_{3}$, cell growth was slower than that of cells treated with eugenol or $1{\alpha},25-dihydroxyvitamin$ $D_{3}$ alone. Eugenol enhanced low dose of $1{\alpha,25-dihydroxyvitamin }$ $D_{3}-induced$ a $G_{0}/G_{1}$ phase arrest in cell cycle. Consistent with this, combined treatment of eugenol and $1{\alpha},25-dihydroxyvitamin$ $D_{3}$ cooperatively increased p27 level and decreased cyclin A, cdk 2 and cdk 4 levels, which are cell cycle regulators related to $G_{0}/G_{1}$ arrest. According to flow cytometric analysis, the expression of CD14 (monocytic differentiation marker) was more increased in the cells co-treated with eugenol and $1{\alpha},25-dihydroxyvitamin$ $D_{3}$. These results indicate that eugenol potentiates cell differentiation mediated by $1{\alpha},25-dihydroxyvitamin$ $D_{3}$ of suboptimal concentration. The differentiation-inducing property of eugenol maybe contributes to chemopreventive activity of cancer.

References

  1. Abe, E., C. Miyaura. H. Sakagami, M. Takeda, K. Konno, T. Yamazaki, S. Yoshiki and T. Suda. 1981. Differentiation of mouse myeloid leukemia cells induced by 1 alpha,25-dihydroxyvitamin D3. Proc. Natl. Acad. Sci. USA 78, 4990-4994 https://doi.org/10.1073/pnas.78.8.4990
  2. Douer, D. 2002. Advances in the treatment of relapsed acute promyelocytic leukemia. Acta Haematol. 107, 1-17 https://doi.org/10.1159/000046623
  3. Evans, R. M. 1988. The steroid and thyroid hormone receptor superfamily. Science 13, 889-895
  4. Ghosh, R., N. Nadiminty, J. E. Fitzpatrick, W. L. Alworth, T. J. Slaga and A. P. Kumar. 2005. Eugenol Causes Melanoma Growth Suppression through Inhibition of E2F1 Transcriptional Activity. J. Biol. Chem. 280, 5812-5819 https://doi.org/10.1074/jbc.M411429200
  5. Huang, M. E., Y. C. Ye, S. R. Chen, J. R. Chai, J. X. Lu, L. Zhoa, L. J. Gu and Z. Y. Wang. 1988. Use of all-trans retinoic acid in the treatment of acute promyelocytic leukemia. Blood 72, 567-572
  6. Inoue, T., J. Kamiyama and T. Sakai. 1999. Sp1 and NF-Y synergistically mediate the effect of vitamin D(3) in the p27(Kip1) gene promoter that lacks vitamin D response elements. J. Biol. Chem. 274, 32309-32317 https://doi.org/10.1074/jbc.274.45.32309
  7. Jung, S. J., Y. Y. Lee, S. Pakkala, S. de Vos, E. Elstner, A. W. Norman, J. Green, M. Uskokovic and H. P. Koeffler. 1994. $1,25(OH)_{2}$-16ene-vitamin D3 is a potent antileukemic agent with low potential to cause hypercalcemia. Leuk. Res. 18, 453-463 https://doi.org/10.1016/0145-2126(94)90081-7
  8. Mangelsdorf, D. J., H. P. Koeffler, C. A. Donaldson, J. W. Pike and M. R Haussler. 1984. 1,25-Dihydroxyvitamin D3-induced differentiation in a human promyelocytic leukemia cell line (HL-60): receptor-mediated maturation to macrophage-like cells. J. Cell Biol. 98, 391-398 https://doi.org/10.1083/jcb.98.2.391
  9. Mistry, A. R., E. W. Pedersen, E. Solomon and D. Grimwade. 2003. The molecular pathogenesis of acute promyelocytic leukaemia: implications for the clinical management of the disease. Blood Rev. 17, 71-97 https://doi.org/10.1016/S0268-960X(02)00075-9
  10. Miyauchi, J. 1999. All-trans retinoic acid and hematopoietic growth factors regulating the growth and differentiation of blast progenitors in acute promyelocytic leukemia. Leuk. Lymphoma 33, 267-280 https://doi.org/10.3109/10428199909058426
  11. Mu, Z. M., K. V. Chin, J. H. Liu, G. Lozano and K. S. Chang. 1994. PML, a growth suppressor disrupted in acute promyelocytic leukemia. Mol. Cell. Biol. 14, 6858-6867 https://doi.org/10.1128/MCB.14.10.6858
  12. Tallman, M. S., J. W. Andersen, C. A Schiffer, F. R Appelbaum, J. H. Feusner, A. Ogden, L. Shepherd, C. Willman, C. D. Bloomfield, J. M. Rowe and P. H. Wiernik. 1997. All-trans-retinoic acid in acute promyelocytic leukemia. N. Engl. J. Med. 337, 1021-1028 https://doi.org/10.1056/NEJM199710093371501
  13. Verstuyf, A., C. Mathieu, L. Verlinden, M. Waer, B. K. Tan and R Bouillon. 1995. Differentiation induction of human leukemia cells (HL60) by a combination of 1,25-dihydroxyvitamin D3 and retinoic acid (all trans or 9-cis). J. Steroid Biochem. Mol. Biol. 53, 431-441 https://doi.org/10.1016/0960-0760(95)00089-I
  14. Wang, Q., J. S. Harrison, M. Uskokovic, A Kutner and G. P. Studzinski. 2005. Translational study of vitamin D differentiation therapy of myeloid leukemia:effects of the combination with a p38 MAPK inhibitor and an antioxidant. Leukemia 19, 1812-1817 https://doi.org/10.1038/sj.leu.2403916
  15. Wang, Q., H. Salman, M. Danilenko and G. P. Studzinski. 2005. Cooperation between antioxidants and 1,25-Dihydroxyvitamin D3 in induced of leukemia HL60 cell differentiation through the JNK/ AP-1/Egr-1 pathway. J. Cell. Physiol. 204, 964-974 https://doi.org/10.1002/jcp.20355
  16. Yoo, C. B., K. T. Han, K. S. Cho, J. Ha, H. J. Park, J. H. Nam, U. H. Kil and K. T. Lee. 2005. Eugenol isolated from the essential oil of Eugenia caryophyllata induces a reactive oxygen species-mediated apoptosis in HL-60 human promyelocytic leukemia cells. Cancer Lett. 224, 41-52
  17. Zhou, G. B., S. J. Chen and Z. Chen. 2005. Acute promyelocytic leukemia: a model of molecular target based therapy. Hematology 10, 270-280 https://doi.org/10.1080/10245330512331390519
  18. Umesono, K., K. K. Murakami, C. C. Thompson and R M. Evans. 1991. Direct repeats as selective response elements for the thyroid hormone, retinoic acid, and vitamin D3 receptors. Cell 65, 1255-1266 https://doi.org/10.1016/0092-8674(91)90020-Y