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Gnidilatimonoein fromDaphne mucronata induces differentiation and apoptosis in leukemia cell lines

Abstract

Gnidilatimonoein is a new diterpene ester, recently isolated from the leaves ofDaphne macronata with potent anti-tumoral and anti-metastastic activities (Yazdanparastet al., 2004). Promyeloblastic (KG1), promyelocytic (NB4) and promonocytic (U937) cells were cultured in the presence of various concentrations of the drug (0.5-3.0 μM) for 3 days. Herein, we report that gnidilatimonoein induces differentiation and apoptosis in KG1, NB4 and U937 cells. The drug inhibited growth and proliferation of KG1, NB4 and U937 cells with IC50 values of 1.5, 1.5 and 1.0 μM, respectively, after 72 h of treatment. Cell viability was also decreased by 18%, 20% and 23%, respectively, after 72 h treatment with the drug. NBT reducing assay revealed that the inhibition of proliferation is associated with differentiation especially toward monocytes-like morphology. Indeed, the drug at 0.5-1.5 μM induced differentiation by 5-50% in the cells. Acridine orange/ethidium bromide (AO/EtBr) double staining and DNA fragmentation assays revealed that apoptosis occurred after differentiation of the cells. Based on the present data, it seems that the new compound is a good candidate for further evaluation as an effective chemotherapeutic agent acting through induction of differentiation and apoptosis.

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References

  1. Bruserud, O. and Gjertsen, B. T., New strategies for the treatment of acute myelogenous leukemia: differentiation induction-present use and future possibilities.Stem Cells, 18, 157–165(2000).

  2. Collins, S. J., Ruscetti, F. W., Gallagher, R. E., and Gallo, R. C, Terminal differentiation of human promyelocytic leukemia cells induced by dimethylsulfoxide and other polar compounds.Proc. Natl. Acad. Sci. U.S.A., 75, 2458–2462 (1978).

  3. Collins, S.J., The HL-60 promyelocytic leukemia cell line: proliferation, differentiation, and cellular oncogene expression.Blood, 70, 1233–1244 (1987).

  4. Hall, I. H., Kasai, R., Wu, R. Y, Tagahara, K., and Lee, K. H., Antitumor agents LV: Effects of genkwadaphnin and yuanhuacine on nucleic acid synthesis of P-338 lymphocytic leukemia cells.J. Pharm. Sci., 71,1263–1267 (1982).

  5. Hedayati, M., Yazdanparast, R., Fasihi, H., and Azizi, F., Antitumor activity of D. mucronata extract and its effects on TNF-a receptors and TNF-a release in cultured human monocytes.Pharma. Biol., 41,194–198 (2003).

  6. Inai, K., Tsutani, H., Yumauchi, T., Fukushima, T, Iwasaki, H., Imamura, S., Wano, Y, Nemoto, Y, Naiki, H., and Ueda, T, Differentiation induction in non-lymphocytic leukemia cells upon treatment with mycophenolate mofetil.Leuk. Res., 24, 761–768(2000).

  7. Jayaram, H. N., Cooney, D. A., Grusch, M., and Krupitza, G, Consequences of IMP dehydrogenase inhibition, and its relationship to cancer and apoptosis.Cure. Med. Chem., 6, 561–574(1999).

  8. Kawaii, S., Tomono, Y, Katase, E., Ogawa, K., Yano, M., Takemura, Y, Ju-ichi, M., Ito, C, and Furukawa H., Acridones as inducers of HL-60 cell differentiation.Leuk. Res., 23, 263–269(1999).

  9. Kerr, J. F., Winterford, C. M., and Harmon, B. Y, Apoptosis: Its significance in cancer and cancer therapy.Cancer, 73, 2013–2026(1994).

  10. Koeffler, H. P., Bar-Eli, M., and Territo, M. C, Phorbol ester effect on differentiation of human myeloid leukemia cell lines blocked at different stages of maturation.Cancer Res., 41, 919–926(1981).

  11. Koeffler, H. P., Induction of differentiation of human acute myelogenous leukemia cells: therapeutic implications.Blood, 62,709–721 (1983).

  12. Martin, S. J., Bradley, J. G, and Cotter, T. G, HL-60 cells induced to differentiate toward neutrophils subsequently dievia apoptosis.Clin. Exp. Immunol., 79,448–453 (1990).

  13. Sachs, L., The control of hematopoiesis and leukemia: from basic biology to the clinic. Proc.Natl. Acad. Sci. U.S.A., 93, 4742–4749(1996).

  14. Sakashita, A., Nakamaki, T, Tsuruoka, N., Honma, Y, and Hozumi, M., Granulocyte colony stimulating factor, not granulocyte-macrophage colony-stimulating factor, cooperates with retinoic acid on the induction of functional N-formyl-methionyl-phenylalanine receptors in HL-60 cells.Leukemia, 5, 26–31 (1991).

  15. Shu, Y Z., Recent natural products based drug development: a pharmaceutical industry perspective.J. Nat. Prod., 61, 1053–1071 (1998).

  16. Spector, D. L, Goldman, R. D., and Leninwand, L. A., Cell a laboratory manual.Cold spring Harbor laboratory press, New York, Volume 1, section. 15/6 (1998).

  17. Stanoeva, E., He, W., and De Kimpe, N., 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(2005).

  18. Watson, R. W., Rotstein, O. D., Parodo J., Bitar R., Hackam D., and Marshall J. C, Granulocytic differentiation of HL-60 cells results in spontaneous apoptosis mediated by increased caspase expression.FEBS Lett., 412, 603–609 (1997).

  19. Yamada, T, Okajima, F., Akbar, M., Tomura, H., Narita, T, Yamada, T, Ohwada, S., Morishita, Y, and Kondo, Y, Cell cycle arrest and the induction of apoptosis in pancreatic cancer cells exposed to adenosine triphosphate in vitro.Oncol. Rep., 9, 113–117 (2002).

  20. Yazdanparast, R. and Sadeghi, H., Antineoplastic effects ofDaphne mucronata: inhibition of DNA and RNA synthesis.Act. Med. Iranica, 41, 202–206 (2003).

  21. Yazdanparast, R. and Sadeghi, H., Nucleic acid synthesis in cancerous cells under the effect of gnidilatimonoein fromDaphne mucronata.Life Sci., 74,1869–1876 (2004).

  22. Yazdanparast, R., Moosavi, M. A., Mahdavi, M., and Sanati, M. H, 3-Hydrogenkwadaphnin fromDendrostellera lessertii induces differentiation and apoptosis in HL-60 Cells.Planta medica, 71,1112–1117(2005).

  23. Zhao, W., Entschiaden, F., Liu, H., Niggemann, B., Fang, Q., Zaenker, K. S., and Han, R., Boswellic acid acetate induces differentiation and apoptosis in highly metastatic melanoma and fibrosarcoma cells.Cancer Detect. Prey., 27, 67–75 (2003).

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Correspondence to Majid Mahdavi or Razieh Yazdanparast.

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Mahdavi, M., Yazdanparast, R. Gnidilatimonoein fromDaphne mucronata induces differentiation and apoptosis in leukemia cell lines. Arch Pharm Res 30, 177–181 (2007). https://doi.org/10.1007/BF02977692

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Key words

  • Apoptosis
  • Daphne mucronata
  • Differentiation
  • KG1 cells
  • Leukemia
  • NB4 cells
  • U937 cells