BMB Reports

Korean Society for Biochemistry and Molecular Biology (생화학분자생물학회)
권호 표지
DOI QR코드

DOI QR Code

The Cytotoxic and Anti-proliferative Effects of 3-Hydrogenkwadaphnin in K562 and Jurkat Cells Is Reduced by Guanosine

  • Published : 2005.07.31
Download PDF
⟨ Previous Next ⟩

Abstract

3-hydrogenwadaphnin (3-HK) is a new daphnane-type diterpene ester isolated from Dendrostellera lessertii with strong anti-tumoral activity in animal models and in cultures. Here, prolonged effects of this new agent on proliferation and viability of several different cancerous cell lines were evaluated. Using [$^3H$]thymidine incorporation, it was found that the drug inhibited cell proliferation and induced G1/S cell cycle arrest in leukemic cells 24 h after a single dose treatment. The cell viability of Jurkat cells was also decreased by almost 10%, 31% and 40% after a single dose treatment (7.5 nM) at 24, 48 and 72 h, respectively. The drug-treated cells were stained with acridine orange/ethidium bromide to document the chromatin condensation and DNA fragmentation. These observations were further confirmed by detection of DNA laddering pattern in the agarose gel electrophoresis of the extracted DNA from the treated cells. Treatment of K562 cells with the drug at 7.5, 15 and 30 nM caused apoptosis in 25%, 45% and 65% of the cells, respectively. Exogenous addition of $25-50\;{\mu}M$ guanosine and/or deoxyguanosine to the cell culture of the drug-treated cells restored DNA synthesis, released cell arrest at G1/S checkpoint and decreased the apoptotic cell death caused by the drug. These observations were not made using adenosine. However, the drug effects on K562 cells were potentiated by hypoxanthine. Based on these observations, perturbation of GTP metabolism is considered as one of the main reasons for apoptotic cell death by 3-HK.

Keywords

References

  1. Ahmed, N. and Weidemann, M. J. (1995) Biochemical effect of three different inhibitors of purine/pyrimidine metabolism on differentiation in HL-60 cells. Leuk Res. 19, 263-273 https://doi.org/10.1016/0145-2126(94)00158-7
  2. Batiuk, T. D., Schnizlein-Bick, C., Plotkin, Z. and Dagher, P. C. (2001) Guanine nucleosides and Jurkat cell death: roles of ATP depletion and accumulation of deoxyribonucleotides. Am. J. Physiol. Cell. Physiol. 281, 1776-1784
  3. Catapano, C. V., Dayton, J. S., Mitchell, B. S. and Fernandes, D. J. (1995) GTP depletion induced by IMP dehydrogenase inhibitors blocks RNA-primed DNA synthesis. Mol. Pharmacol. 47, 948-955
  4. Cohen, M. B., Maybaum, J. and Sadee, W. (1981) Guanine nucleotide depletion and toxicity in mouse T lymphoma (S-49) cells. J. Biol. Chem. 256, 8713-8717
  5. Earnshaw, W. C., Martins, L. M. and Kaufmann, S. H. (1999) Mammalian caspases: structure, activation, substrates, and functions during apoptosis. Annu. Rev. Biochm. 68, 383-424 https://doi.org/10.1146/annurev.biochem.68.1.383
  6. Evans, F. J. and Soper, C. J. (1978) The tigliane, daphnane and ingenane diterpenes, their chemistry, distribution and biological activities. Lloydia. 41, 193-233
  7. Gu, J. J., Gathy, K., Santiago, L., Chen, E., Huang, M., Graves, L. M. and Mitchell, B. S. (2003) Induction of apoptosis in IL-3-dependent hematopoietic cell lines by guanine nucleotide depletion. Blood. 101, 4958-4965 https://doi.org/10.1182/blood-2002-08-2547
  8. Hall, I. H., Kasai, R., Wu, R. Y., Tagahara, K. and Lee, K. H. (1982) Antitumor agents LV: Effects of genkwadaphnin and yuanhuacine on nucleic acid synthesis of P-388 lymphocytic leukemia cells. J. Pharm. Sci. 71, 1263-1267 https://doi.org/10.1002/jps.2600711120
  9. Hall, I. H., Liou, Y. F., Oswald, C. B. and Lee, K. H. (1986) The effects of genkwadaphnin and genidilatidin on the growth of P-338, L-1210 leukemia and KB carcinoma cells in vitro. Eur. J. Cancer. Clin. Oncol. 22, 45-52 https://doi.org/10.1016/0277-5379(86)90341-X
  10. Hedayati, M., Yazdanparast, R., Fasihi, H. and Azizi, F. (2002) Anti-tumor activity of Daphne mucronata extract and its effects on TNF-$\alpha$ receptors and TNF-$\alpha$ release in culture human monocytes. Pharmaceutical. Biol. 41, 194-198 https://doi.org/10.1076/phbi.41.3.194.15093
  11. Jayaram, H. N., Gharehbaghi, K., Jayaram, N. H., Rieser, J., Krohn, K. and Paull, K. D. (1992) Cytotoxicity of a new IMP dehydrogenase inhibitor, benzamide riboside, to human myelogenous leukemia K562 cells. Biochem. Biophys. Res. Commun. 186, 1600-1606 https://doi.org/10.1016/S0006-291X(05)81591-8
  12. Jayaram, H. N., Cooney, D. A., Grusch, M. and Krupitza, G. (1999) Consequences of IMP dehydrogenase inhibition, and its relationship to cancer and apoptosis. Curr. Med. Chem. 6, 561-574
  13. Kupchan, S. M., Shizuri, Y., Sumner, W. C., Haynes, H. R., Leighton, A. P. and Sickles, B. R. (1976) Isolation and structural elucidation of new potent antileukemic diterpenoid esters from Ginida species. J. Org. Chem. 41, 3850-3853 https://doi.org/10.1021/jo00886a016
  14. Laliberte, J., Yee, A., Xiong, Y. and Mitchell, B. S. (1998) Effects of guanine nucleotide depletion on cell cycle progression in human T lymphocytes. Blood. 91, 2896-2904
  15. Li, G., Segu, V. B., Rabaglia, M. E., Luo, R. H., Kowluru, A. and Metz, S. A. (1998) Prolonged depletion of guanosine triphosphate induces death of insulin-secreting cells by apoptosis. Endocrinology 139, 3752-3762 https://doi.org/10.1210/en.139.9.3752
  16. Liou, Y. F., Hall, I. H. and Lee, K. H. (1982) Antitumor agents LVI: the protein synthesis inhibition by genkwadaphnin and yuanhuacine of P-388 lymphocytic leukemia cells. J. Pharm. Sci. 71, 1340-1344 https://doi.org/10.1002/jps.2600711208
  17. McGahon, A., Bissonnette, R., Schmitt, M., Cotter, K. M., Green, D. R. and Cotter, T. G. (1994) BCR-ABL maintains resistance of chronic myelogenous leukemia cells to apoptotic cell death. Blood. 83, 1179-1187
  18. Metz, S., Holland, S., Johnson, L., Espling, E., Rabaglia, M., Segu, V., Brockenbrough, J. S. and Tran, P. O. (2001) Inosine-5'-monophosphate dehydrogenase is required for mitogenic competence of transformed pancreatic beta cells. Endocrinology 142, 193-204 https://doi.org/10.1210/en.142.1.193
  19. Mianabadi, M., Rivera, E. and Yazdanparast, R. (2003) Characterization of a new diterpene ester from the leaves of D. mucronata. J. Trop. Med. Plants. 4, 1-4
  20. Mianabadi, M. and Yazdanparast, R. (2004) Inhibition of substrate-tumor cell adhesion under the effect of gnidilatimonoein purified from Daphne mucronata. Am. J. Chin. Med. 32, 369-376 https://doi.org/10.1142/S0192415X04002028
  21. Nio, Y., Imai, S., Shiraishi, T., Tsubono, M., Morimoto, H., Tseng, C. C. and Tobe, T. (1990) Chemosensitivity correlation between the primary tumors and simultaneous metastatic lymph nodes of patients evaluated by DNA synthesis inhibition assay. Cancer 65, 1273-1278 https://doi.org/10.1002/1097-0142(19900315)65:6<1273::AID-CNCR2820650603>3.0.CO;2-O
  22. Papazisis, K. T., Zambouli, D., Kimoundri, O. T., Papadakis, E. S., Vala, V., Geromichalos, G. D., Voyatzi, S., Markala, D., Destouni, E., Boutis, L. and Kortsaris, A. H. (2000) Protein tyrosine kinase inhibitor, genistein, enhances apoptosis and cell cycle arrest in K562 cells treated with gamma-irradiation. Cancer Lett. 160, 107-113 https://doi.org/10.1016/S0304-3835(00)00569-3
  23. Pezzuto, J. M. (1997) Plant-derived anticancer agents. Biochem. Pharmacol. 53, 121-133 https://doi.org/10.1016/S0006-2952(96)00654-5
  24. Pipaon, C., Gutierrez, P., Montero, J. C., Lorenzo, M., Eguiraun, A., De La Fuente, J. A., Pandiella, A., Leon, J. and Ortiz, J. M. (2002) Mitogen-activated protein kinase routes as targets in the action of diaza-anthracene compounds with a potent growth-inhibitory effect on cancer cells. Mol. Cancer. Ther. 1, 811-819
  25. Sadeghi, H. and Yazdanparast, R. (2003) Effect of Dendrostellera lessertii on the intracellular alkaline phosphatase activity of four human cancer cell lines. J. Ethnopharmacol. 86, 11-14 https://doi.org/10.1016/S0378-8741(02)00380-X
  26. Saydam, G., Aydin, H. H., Sahin, F., Selvi, N., Oktem, G., Terzioglu, E., Buyukkececi, F. and Omay, S. B. (2003) Involvement of protein phosphatase 2A in interferon-alpha-2binduced apoptosis in K562 human chronic myelogenous leukemia cells. Leuk Res. 27, 709-717 https://doi.org/10.1016/S0145-2126(02)00347-8
  27. Shu, Y. Z. (1998) Recent natural products based drug development: a pharmaceutical industry perspective. J. Nat. Prod. 61, 1053-1071 https://doi.org/10.1021/np9800102
  28. Stanoeve, E., He, W. and De Kimpe, N. (2005) Natural and synthetic cage compounds incorporating the 2,9,10-trioxatricyclo 4.3.1.03,8 decane type moiety. Bioorg. Med. Chem. 13, 17-28 https://doi.org/10.1016/j.bmc.2004.07.070
  29. Taraphdar, A. K., Roy, M. and Bhattacharya, R. K. (2001) Natural products as inducers of apoptosis: implication for cancer therapy and preventation. Curr. Sci. 80, 1387-1396
  30. Vistica, D. T., Skehan, P., Scudiero, D., Monks, A., Pittman, A. and Boyd, M. R. (1991) Tetrazolium-based assays for cellular viability: a critical examination of selected parameters affecting formazan production. Cancer Res. 51, 2515-2520
  31. Vitale, M., Zamai, L., Falcieri E., Zauli, G., Gobbi, P., Santi, S., Cinti, C. and Weber, G. (1997) IMP dehydrogenase inhibitor, tiazofurin, induces apoptosis in K562 human erythroleukemia cells. Cytometry. 30, 61-66 https://doi.org/10.1002/(SICI)1097-0320(19970215)30:1<61::AID-CYTO9>3.0.CO;2-I
  32. Yamada, T., Okajama, F., Akbar, M., Tomura, H., Narita, T., Yamada, T., Ohwada, S., Morishita, Y. and Kondo, Y. (2002) Cell cycle arrest and the induction of apoptosis in pancreatic cancer cells exposed to adenosine triphosphate in vitro. Oncol Rep. 9, 113-117
  33. Yazdanparast, R., Mianabadi, M. and Abdolmohammadi, M. H. (2003) Anti-tumor activity of Dendrostellera lessertii and the inhibitory effect of one of its purified diterpene ester on wehi-164 cell adhesion. Nat. Prod. Sci. 9, 161-166
  34. Yazdanparast, R. and Mianabadi, M. (2004) The effect of the active component of Dendrostellera lessertii on the adhesive property of human platelets and HL-60 cells. Life Sci. 75, 733-739 https://doi.org/10.1016/j.lfs.2004.01.016
  35. Yazdanparast, R. and Sadeghi, H. (2004) Nucleic acid synthesis in cancerous cells under effect of gnidilatimonoein from Daphne mucronata. Life Sci. 74, 1869-1876 https://doi.org/10.1016/j.lfs.2003.08.039
  36. Yoshida, M., Feng, W., Saijo, N. and Ikekawa, T. (1996) Antitumor activity of daphnane-type diterpene gnidimacirin isolated from Stellera chamaejasme. Int. J. Cancer. 66, 268-273 https://doi.org/10.1002/(SICI)1097-0215(19960410)66:2<268::AID-IJC22>3.0.CO;2-7
  37. Zhang, G., Tu, C., Zhang, G., Zhou, G. and Zheng, W. (2000) Indomethacin induces apoptosis and inhibits proliferation in chronic myeloid leukemia cells. Leuk Res. 24, 385-392 https://doi.org/10.1016/S0145-2126(99)00198-8
  38. Zimmermann, A. G., Gu, J. J., Laliberte, J. and Mitchel, B. S. (1998) Inosine-5'-monophosphate dehydrogenase: regulation of expression and role in cellular proliferation and T lymphocytes activation. Prog. Nucleic. Acid. Res. Mol. Biol. 61, 181-209 https://doi.org/10.1016/S0079-6603(08)60827-2

Cited by

  1. Distinct MAPK signaling pathways, p21 up-regulation and caspase-mediated p21 cleavage establishes the fate of U937 cells exposed to 3-hydrogenkwadaphnin: Differentiation versus apoptosis vol.230, pp.1, 2008, https://doi.org/10.1016/j.taap.2008.02.010
  2. Antimelanogenesis effect of Tunisian herb Thymelaea hirsuta extract on B16 murine melanoma cells vol.16, pp.12, 2007, https://doi.org/10.1111/j.1600-0625.2007.00618.x
  3. 3-Hydrogenkwadaphnine, a novel diterpene ester from Dendrostellera lessertii, its role in differentiation and apoptosis of KG1 cells vol.16, pp.2-3, 2009, https://doi.org/10.1016/j.phymed.2008.07.014
  4. Cytotoxic Activity from Curcuma zedoaria Through Mitochondrial Activation on Ovarian Cancer Cells vol.29, pp.4, 2013, https://doi.org/10.5487/TR.2013.29.4.257
  5. Antiproliferative Activity of the Isofuranonaphthoquinone Isolated fromBulbine frutescensagainst Jurkat T Cells vol.2014, 2014, https://doi.org/10.1155/2014/752941
  6. Cytotoxicity Evaluation of Essential Oil and its Component fromZingiber officinaleRoscoe vol.32, pp.3, 2016, https://doi.org/10.5487/TR.2016.32.3.225
  7. Intracellular GTP level determines cell's fate toward differentiation and apoptosis vol.253, pp.3, 2011, https://doi.org/10.1016/j.taap.2011.02.021