Decursin from Angelica gigas Nakai Promotes Cytotoxicity and Induces Apoptosis in THP-1 cells, a Human Acute Monocytic Leukemia

당귀로부터 정제한 Decursin의 인간 급성 단핵구성 백혈병 세포(THP-1 cells)의 세포 독성 및 Apoptosis에 미치는 영향

  • Received : 2016.05.03
  • Accepted : 2016.08.16
  • Published : 2016.09.30


Decursin is a major component of the root of Angelica gigas(Umbelliferae), which has been traditionally used in Korea as a tonic and to treat anemia, hemiplegia, and women's diseases. The objective of this study is to identify the anti-cancer mechanism induced by decursin on apoptosis of human leukemia and lymphoma cells. Cytotoxicity of decursin on U937, HL-60, MOLT-4, THP-1 cells showed the significant effects. First of all, $IC_{50}$ of decursin on four cell lines was 27.1, 32.4, 17.4, $15.1{\mu}M$, respectively. So $IC_{50}$ in THP-1 cells was the smallest among 4 cell lines treated with decursin($15.1{\mu}M$). In order to understand the apoptosis-mechanism by decursin, we examined the gene expression of bcl-2(anti-apoptotic), bax(pro-apoptotic) and p53(tumor suppressor)after treating the THP-1 cells with decursin(10, 50 and $100{\mu}M$). It was found bcl-2 gene was decreased dose dependently, the expression level of bax gene of THP-1 cells treated with $100{\mu}M$ of decursin was about 3 times higher than those of control, and p53 gene was increased In the same concentration($100{\mu}M$), p53 gene was increased dose dependent manner. In protein express, bcl-2 and p53 protein showed a tendency to decrease. bax was increased about 4 fold. Therefore decursin is a useful chemotherapeutic agent against leukemia.


  1. 국립암센터 (2014) Annual report of cancer statistics in Korea in 2012. National Cancer center 1-179.
  2. Cho, Y. J. and Hou, W. N. (2005) Effects of dietary bong-ip (Morus alba L.), gam-chei (Glycyrrhiza glabra), sol-ip (Pinus densiflora) and dang-gi (Angelica gigas) on serum composition in rats. Korean J. Food culture 20: 123-129.
  3. Han, E. J., Roh, S. B. and Bae, S. J. (2000) Effects of quinone reductase induction and cytoxicity of the Angelica radix extracts. J. Korean Soc. Food Sci. Nutr. 29: 147-152.
  4. Kim, J. H., Kim, D. H., You, J. H., Kim, C. H., Kwon, M. C., Seong N. S., Lee, S. E. and Lee H. Y.(2005) Immuno-regulatory activ?ties of various fractions from Ehpedrae sinica Stapf, Rubus Coreanus Miq. and Angelica gigas nakai extracts with untrasonification. Korean J. Medicinal Crop. Sci. 13: 161-170.
  5. Wessler, S., Kleiger, R. E., Cornfield, J. and Teitelbaum, S. L. (1974) Coumarin theraphy in acute myocardial infarction. A hobson's choice. Arch. Intem. Med. 134: 774-779.
  6. Ristola, P. and Pyorala, K. (1972) Determinants of the response to coumarin anticoagulants in patients with acute myocardial infarction. Ata. Med. Scand. 192: 183-188.
  7. Kang, S. Y., Lee, K. Y., Sung, S. H., Park, M. J. and Kim, Y. C. (2001) Coumarins isolated from Angelica gigas inhibit acetylcholine esterase: structure-activity relationships. J. Nat. Prod. 64: 683-685.
  8. Kang, S. Y., Lee, K. Y., Park, M. J., Kim, Y. C., Markelonis, G. J., Oh, T. H. and Kim, Y. C. (2003) Decursin from Angelica gigas mitigates amnesia induced by scopolamine in mice. Neurobiol. Learn. Mem. 79: 11-18.
  9. Kim, J. H., Jeong, J. H., Jeon, S. T., Kim, H., Ock, J., Suk, K., Kim, S. I., Song, K. S. and Lee, W. H. (2006) Decursin inhibits induction of inflammatory mediators by blocking nuclear factor-kappaB activation in macrophages. Mol. Pharmacol. 69: 1783-1790.
  10. Son, S. H., Park, K. K., Park, S. K., Kim, Y. C., Kim, Y. S., Lee, S. K. and Chung, W. Y. (2011) Decursin and decursinol from Angelica gigas inhibit the lung metastasis of murine colon carcinoma. Phytother Res. 25: 959-964.
  11. Yim, D., Singh, R. P., Agarwal, C., Lee, S. and Chi, H. and Agarwal, R. (2005) A novel anticancer agent, decursin, induces G1 arrest and apoptosis in human prostate carcinoma cells. Cancer Res. 1; 65: 1035-1044.
  12. Kim, J. H., Jeong, S. J., Kwon, H. Y., Park, S. Y., Lee, H. J., Lee, H. J., Lieske, J. C. and Kim, S. H. (2010) Decursin prevents cisplatin-induced apoptosis via the enhancement of antioxidant enzymes in human renal epithelial cells. Biol. Pharm. Bull. 33: 1279-1284.
  13. Li, L., Li, W., Jung, S. W., Lee, Y. W. and Kim, Y. H. (2011) Protective effects of decursin and decursinol angelate against amyloid ${\beta}$-protein-induced oxidative stress in the PC12 cell line: the role of Nrf2 and antioxidant enzymes. Biosci. Biotechnol. Biochem. 75: 434-442.
  14. Park, K. W., Choi, S. R., Shon, M. Y., Jeong, I. Y., Kang, K. S., Lee, S. T., Shim, K. H. and Seo, K. I. (2007) Cytotoxic effects of decursin from Angelica gigas Nakai in human cancer cells. J. Korea Soc. Food Sci. Nutr. 36: 1385-1390.
  15. Lee, K. Y., Sung, S. H. and Kim, Y. C. (2008) Cognitiveenhancing activity of decursin derivatives. Kor. J. pharmacogn. 39: 86-90.
  16. Lee, S., Shin, D. S., Kim, J. S., Oh, K. B. and Kang, S. S. (2003) Antibacterial coumarins from Angelica gigas roots. Arch. Pharm. Res. 26: 449-452.
  17. Bae, E. A., Han, M. J., Kim, N. J. and Kim, D. H. (1998) Anti-Helicobacter pylory activity of herbal medicines. Biol. Pharm. Bull. 21: 990-992.
  18. Lee, Y. Y., Lee, S., Jin, J. L. and Yun-Choi, H. S. (2003) Platelet anti-aggregatory effects of coumarins from the roots of Angelica genuflexa and A. gigas. Arch. Pharm. Res. 26: 723-726.
  19. Lee, S. H., Lee, Y. S., Jung, S. H., Shin, K. H., Kim, B. K. and Kang, S. S. (2003) Antioxidant activities of decursinol angelate and decursin from angelica gigas roots. Nat. Prod. Sci. 9: 170-173.
  20. Park, K. W., Choi, S. R., Shon, M. Y., Jeong, I. Y., Kang, K. S., Lee, S. T., Shim, K. H. and Seo, K. I. (2007) Cytotoxic effects of decursin from Angelica gigas Nakai in human cancer cells. J. Korean Soc. Food Sci. Nutr. 36: 1385-1390.
  21. Kim, B. S., Seo, H., Kim, H. J., Bae, S. M., Son, H. N., Lee, Y. J., Ryu, S., Park, R. W. and Nam, J. O. (2015) Decursin from Angelica gigas Nakai inhibits B16F10 melanoma growth through induction of apoptosis. J. Med. Food 18b 1121-1127.
  22. Li, L., Du, J., Zou, L., Xia, H., Wu, T., Kim, Y. and Lee, Y. (2015) The neuroprotective effects of decursin isolated from Angelica gigas Nakai against amyloid ${\beta}$-protein-induced apoptosis in PC12 cells via a mitochondria-related caspase pathway. Neurochem. Res. 40: 1555-1562.
  23. Kim, H. H., Ahn, K. S., Han, H., Choung, S. Y., Choi, S. Y. and Kim, I. H. (2005) Decursin and PDBu: Two PKC activators distinctively acting in the megakaryocytic differentiation of K562 human erythroleukemia cells. Leuk. Res. 29: 1407-1413.
  24. Kim, H. H., Bang, S. S., Choi, J. S., Han, H. and Kim, I. H. (2005) Involvement of PKC and ROS in the cytotoxic mechanism of anti-leukemic decursin and its derivatives and their structure-activity relationship in human K562 erythroleukemia and U937 myeloleukemia cells. Cancer Lett. 223: 191-201.
  25. Ahn, Q., Jeong, S. J., Lee, H. J., Kwon, H. Y., Han, I., Kim, H. S., Lee, H. J., Lee, E. O., Ahn, K. S., Jung, M. H., Zhu, S., Chen, C. Y. and Kim, S. H. (2010) Inhibition of cyclooxygenase- 2-dependent survivin mediates decursin-induced apoptosis in human KBM-5 myeloid leukemia cells. Cancer Lett. 298: 212-221.
  26. Mosmann, T. (1983) Rapid colorimetric assay for cellular growth and survival application to proliferation and cytotoxic assays. J. Immunol. Methods 65: 55-63.
  27. Birch, D. E., Kolmodin, L., Laird, W. J., McKinney, N., Wong, J., Young, K. K. Y., Zangenberg, G. A. and Zoccoli, M. A.(1996) Simplified Hot-Start PCR, Nature 381: 445-446.
  28. Dowdy, S., Weardon, S. and Chilko, D. (2004) Statistics for research (3rd ed). Wiley-interscience, USA 285-287.
  29. Haupt, S., Berger, M., Goldberg, Z. and Haupt, Y. (2003) Apoptosis- the p53 network. J. Cell Sci. 116: 4077-4085.
  30. Dy, G. K. and Adjei, A. A. (2002) Novel targets for lung cancer therapy: part I. J. Clin. Oncol. 20: 2881-2294.
  31. Son, C. Y., Baek, I. H., Song, G. Y., Kang, J. S. and Kwon, K. I. (2009) Pharmacological effect of decursin and decursinol angelate from Angelica gigas Nakai. Yakhak Hoeji 53: 303-313.
  32. Park, K. W., Choi, S. R., Hong, H. R., Kim, J. Y., Shon, M. Y. and Seo, K. I. (2007) Biological activities of methanol extract of Angelica gigas Nakai. Korean J. Food Preserv. 14: 655-661.
  33. Lee, S., Lee, Y. S., Jung, S. H., Shin, K. H., Kim, B. K. and Kang, S. S. (2000) Anti-tumor activities of decursinol angelate and decursin from Angelica gigas. Arch. Pharm. Res. 26: 727-730.