Induction of apoptosis in leukemia cell lines by Linum persicum and Euphorbia cheiradenia


Purpose: In the present study two medicinal herbs Linum persicum and Euphorbia cheiradenia that are native to Iran were tested for their possible anticancer effect and induction of apoptosis on human tumor cell lines including leukemia cell lines. Methods: The effect of methanolic extracts of the herbs on the inhibition of cell proliferation was assessed by MTT colorimetric assay. K562 and Jurkat cell lines treated with the extracts were analyzed for the induction of apoptosis by flow cytometry using propidium iodide staining. DNA fragmentation analysis was performed. Results: Various concentrations of L. persicum and E. cheiradenia showed inhibitory effects on different cell lines. Two leukemic lines including K562 and Jurkat were the most sensitive cells for L. persicum with IC50 of 0.1 and 10 μg/ml, respectively. In the cultures of tumor cell lines treated with E. cheiradenia, the main inhibitory effects was for Jurkat cells with IC50 of 12.5 μg/ml. Results indicated a dose-dependent accumulation of cells in the sub-G1 phase. Study of internucleosomal DNA fragmentation showed a typical DNA laddering in agarose gels for both extracts. Conclusion: The present study showed cytotoxic activity of both herbs on tumor cell lines and suggests that this effect may in part be due to the induction of apoptosis in leukemic cells.

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  1. Adam-Klages S, Adam D, Janssen O, Kabelitz D (2005) Death receptors and caspases: role in lymphocyte proliferation, cell death, and autoimmunity. Immunol Res 33:149–166

    PubMed  Article  CAS  Google Scholar 

  2. Canel C, Moraes RM, Dayan FE, Ferreira D (2000) Podophyllotoxin. Phytochemistry 54:115–120

    PubMed  Article  CAS  Google Scholar 

  3. Corea G, Fattorusso E, Lanzotti V, Taglialatela-Scafati O, Appendino G, Ballero M, Simon PN, Dumontet C, Di Pietro A (2003) Modified jatrophane diterpenes as modulators of multidrug resistance from Euphorbia dendroides L. Bioorg Med Chem 11:5221–5227

    PubMed  Article  CAS  Google Scholar 

  4. Cuendet M, Pezzuto JM (2004) Antitumor activity of bruceantin: an old drug with new promise. J Nat Prod 67:269–272

    PubMed  Article  CAS  Google Scholar 

  5. Gillespie SK, Zhang XD, Hersey P (2004) Ingenol 3-angelate induces dual modes of cell death and differentially regulates tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis in melanoma cells. Mol Cancer Ther 3:1651–1658

    PubMed  CAS  Google Scholar 

  6. Herrmann M, Lorenz HM, Voll R, Grunke M, Woith W, Kalden JR (1994) A rapid and simple method for the isolation of apoptotic DNA fragments. Nucleic Acids Res 22:5506–5507

    PubMed  Article  CAS  Google Scholar 

  7. Heywood VH (1979) Flowering plants of the world. Oxford University Press, Oxford, pp 207–208

    Google Scholar 

  8. Hohmann J, Molnar J, Redei D, Evanics F, Forgo P, Kalman A, Argay G, Szabo P (2002) Discovery and biological evaluation of a new family of potent modulators of multidrug resistance: reversal of multidrug resistance of mouse lymphoma cells by new natural jatrophane diterpenoids isolated from Euphorbia species. J Med Chem 45:2425–2431

    PubMed  Article  CAS  Google Scholar 

  9. Kartal M, Konuklugil B, Indrayanto G, Alfermann AW (2004) Comparison of different extraction methods for the determination of podophyllotoxin and 6-methoxypodophyllotoxin in Linum species. J Pharm Biomed Anal 35:441–447

    PubMed  Article  CAS  Google Scholar 

  10. Kupchan SM, Uchida I, Branfman AR, Dailey RG Jr, Fei BY (1976) Antileukemic principles isolated from Euphorbiaceae plants. Science 191:571–572

    PubMed  Article  CAS  Google Scholar 

  11. Li X, Ji L, Wang Z (2002) Advances in the study on the effects of Chinese herbal drugs on apoptosis. Zhong Yao Cai 25:135–139

    PubMed  CAS  Google Scholar 

  12. Liu LG, Tan RX (2001) New jatrophane diterpenoid esters from Euphorbia turczaninowii. J Nat Prod 64:1064–1068

    PubMed  Article  CAS  Google Scholar 

  13. Liu WK, Ho JC, Qin G, Che CT (2002) Jolkinolide B induces neuroendocrine differentiation of human prostate LNCaP cancer cell line. Biochem Pharmacol 63:951–957

    PubMed  Article  CAS  Google Scholar 

  14. Ogbourne SM, Suhrbier A, Jones B, Cozzi SJ, Boyle GM, Morris M, McAlpine D, Johns J, Scott TM, Sutherland KP, Gardner JM, Le TT, Lenarczyk A, Aylward JH, Parsons PG (2004) Antitumor activity of 3-ingenyl angelate: plasma membrane and mitochondrial disruption and necrotic cell death. Cancer Res 64:2833–2839

    PubMed  Article  CAS  Google Scholar 

  15. Petersen M, Alfermann AW (2001) The production of cytotoxic lignans by plant cell cultures. Appl Microbiol Biotechnol 55:135–142

    PubMed  Article  CAS  Google Scholar 

  16. Ravikanth V, Lakshmi Niranjan Reddy V, Vijender Reddy A, Ravinder K, Prabhakar Rao T, Siva Ram T, Anand Kumar K, Prakesh Vamanarao D, Venkateswarlu Y (2003) Three new ingol diterpenes from Euphorbia nivulia: evaluation of cytotoxic activity. Chem Pharm Bull (Tokyo) 51:431–434

    Article  CAS  Google Scholar 

  17. Rechinger KH (1982) Euphorbiaceae. In: Rechinger KH (ed) Flora iranica, no.6. Akademische Druck-u, Verlagsanstalt, Graz, pp 8–48

  18. Thomson M, Ali M (2003) Garlic [Allium sativum]: a review of its potential use as an anti-cancer agent. Curr Cancer Drug Targets 3:67–81

    PubMed  Article  CAS  Google Scholar 

  19. Tsan MF, White JE, Maheshwari JG, Chikkappa G (2002) Anti-leukemia effect of resveratrol. Leuk Lymphoma 43:983–987

    PubMed  CAS  Google Scholar 

  20. Valente C, Pedro M, Duarte A, Nascimento MS, Abreu PM, Ferreira MJ (2004) Bioactive diterpenoids, a new jatrophane and two ent-abietanes, and other constituents from Euphorbia pubescens. J Nat Prod 67:902–904

    PubMed  Article  CAS  Google Scholar 

  21. Van Uden W, Homan B, Woerdenbag HJ, Pras N, Malingre TM, Wichers HJ, Harkes M (1992) Isolation, purification, and cytotoxicity of 5-methoxypodophyllotoxin, a lignan from a root culture of Linum flavum. J Nat Prod 55:102–110

    PubMed  Article  Google Scholar 

  22. Vasilev NP, Ionkova I (2005) Cytotoxic activity of extracts from Linum cell cultures. Fitoterapia 76:50–53

    PubMed  Article  CAS  Google Scholar 

  23. Vasilev N, Momekov G, Zaharieva M, Konstantinov S, Bremner P, Heinrich M, Ionkova I (2005) Cytotoxic activity of a podophyllotoxin-like lignan from Linum tauricum Willd. Neoplasma 52:425–429

    PubMed  CAS  Google Scholar 

  24. Weiss SG, Tin-Wa M, Perdue RE, Farnsworth NR (1975) Potential anticancer agents II: antitumor and cytotoxic lignans from Linum album (Linaceae). J Pharm Sci 64:95–98

    PubMed  Article  CAS  Google Scholar 

  25. Wu TS, Lin YM, Haruna M, Pan DJ, Shingu T, Chen YP, Hsu HY, Nakano T, Lee KH (1991) Antitumor agents, 119. Kansuiphorins A and B, two novel antileukemic diterpene esters from Euphorbia kansui. J Nat Prod 54:823–829

    PubMed  Article  CAS  Google Scholar 

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This work was supported by grants 81-35 and 83-2090 from Shiraz University of Medical Sciences.

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Correspondence to Zahra Amirghofran.

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Amirghofran, Z., Bahmani, M., Azadmehr, A. et al. Induction of apoptosis in leukemia cell lines by Linum persicum and Euphorbia cheiradenia . J Cancer Res Clin Oncol 132, 427–432 (2006).

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  • Linum persicum
  • Euphorbia cheiradenia
  • Apoptosis