DOI QR코드

DOI QR Code

Purification of Cucurbitacins D, E, and I from Ecballium Elaterium (L.) A. Rich Fruits and Study of Their Cytotoxic Effects on the AGS Cell Line

  • Jafargholizadeh, Naser (Department of Cell and Molecular Biology, School of Biology, College of Science, University of Tehran) ;
  • Zargar, Seyed Jalal (Department of Cell and Molecular Biology, School of Biology, College of Science, University of Tehran) ;
  • Yassa, Narguess (Department of Pharmacognosy, Faculty of Pharmacy, Tehran University of Medical Sciences) ;
  • Tavakoli, Saeed (Department of Pharmacognosy, Faculty of Pharmacy, Tehran University of Medical Sciences)
  • Published : 2016.10.01

Abstract

Background: The plant Ecballium elaterium (L.) A. Rich, belongs to the Cucurbitaceae family which occupies an important position in traditional medicine prescriptions. It has been reported that a freeze-dried aqueous extract of E. elaterium fruits has cytotoxic effects on the AGS human stomach adenocarcinoma cell line. We here focused on anticancer effects of the main chemicals purified from E. elaterium fruits. Materials and Methods: We isolated cucurbitacins D, E, and I from chloroform, and ethyl acetate fractions of a methanolic extract of E. elaterium fruits and assessed their cytotoxic effects on the AGS cell line by MTT assay. The methanolic extract was fractionated to petroleum ether, chloroform, and ethyl acetate fractions. The compounds isolated by column chromatography were identified by NMR spectroscopy. Results: After 24 h of incubation with AGS cells, the IC50 values were 0.3, 0.1, and $0.5{\mu}g/ml$ for cucurbitacins D, E, and I respectively. Conclusions: This finding suggests that because of its cucurbitacins, E. elaterium fruit may have some cytotoxic effects on gastric cancer cells. Also, compared with D and I, cucurbitacin E showed greater potency in this regard.

Keywords

Ecballium elaterium;chromatography;cucurbitacins;gastric cancer;MTT assay

Acknowledgement

Supported by : Iran National Science Foundation (INSF)

References

  1. Attard E, Cuschieri A, Brincat MP (2005). Morphological effects induced by Cucurbitacin E on ovarian cancer cells in vitro. J Natural Remedies, 5, 70-4.
  2. Attard E, Cuschieri A (2004). Cytotoxicity of Cucurbitacin E extracted from Ecballium elaterium in vitro. J Natural Remedies, 4, 137-4.
  3. Attard EG, Scicluna-Spiteri A (2001). Ecballium elaterium: an in vitro source of cucurbitacins. Fitoterapia, 72, 46-3. https://doi.org/10.1016/S0367-326X(00)00256-2
  4. Attard E, Scicluna-Spiteri A (2003). The cultivation and cucurbitacin content of ecballium elaterium (L.) A. Rep Cucurbit Genet Coop , 26, 66-9.
  5. Bohlooli S, Jafari N, Jahed S (2012). Cytotoxic effect of freeze-dried extract of ecballium elaterium fruit on gastric adenocarcinoma (AGS) and esophageal squamous cell carcinoma (KYSE30) cell lines. J Gastrointest Cancer, 43, 579-3. https://doi.org/10.1007/s12029-012-9383-4
  6. Chen JC, Chiu MH, Nie RL, Cordell GA, Qiu SX (2005). Cucurbitacins and cucurbitane glycosides: structures and biological activities. Nat Prod Rep, 22, 386-9. https://doi.org/10.1039/b418841c
  7. Ferlay J, Soerjomataram I, Ervik M, et al (2013). GLOBOCAN 2012 v1.0, Cancer incidence and mortality worldwide: IARC CancerBase No. 11 [Internet]. Lyon: International Agency for Research on Cancer.
  8. Jacquot C, Rousseau B, Carbonnelle D, et al (2014). Cucurbitacin-D-induced CDK1 mRNA up-regulation causes proliferation arrest of a non-small cell lung carcinoma cell line (NSCLC-N6). Anticancer Res, 34, 4797-6.
  9. Kim MJ, Park HJ, Hong MS, et al (2005). Citrus Reticulata blanco induces apoptosis in human gastric cancer cells SNU-668. Nutr Cancer, 51, 78-82. https://doi.org/10.1207/s15327914nc5101_11
  10. Lai CH, Fang SH, Rao YK, et al (2008). Inhibition of Helicobacter pylori-induced inflammation in human gastric epithelial AGS cells by Phyllanthus urinaria extracts. J Ethnopharmacol, 118, 522-6. https://doi.org/10.1016/j.jep.2008.05.022
  11. Lee DH, Iwanski GB, Thoennissen NH (2010). Cucurbitacin: ancient compound shedding new light on cancer treatment. Scientific World J, 10, 413-8. https://doi.org/10.1100/tsw.2010.44
  12. Li CJ, Tsang SF, Tsai CH, et al (2012). Momordica charantia extract induces apoptosis in human cancer cells through caspase- and mitochondria-dependent pathways. Evid Based Complement Alternat Med, Article ID 261971, 11pages.
  13. Li G, Yu K, Li F, et al (2014). Anticancer potential of Hericium erinaceus extracts against human gastrointestinal cancers. J Ethnopharmacol, 153, 521-30. https://doi.org/10.1016/j.jep.2014.03.003
  14. Li WB, Li Y, Yu C, He YM (2015). Reversal of multidrug resistance by the chinese medicine yiqi jianpi huaji decoction and the mechanism of action in human gastric cancer SGC7901/VCR Cells. evid based complement alternat Med, Article ID 390812, 11 pages.
  15. Newman DJ, Cragg GM (2012). Natural products as sources of new drugs over the 30 years from 1981 to 2010. J Nat Prod, 75, 311-35. https://doi.org/10.1021/np200906s
  16. Rios JL, Andujar I, Escandell JM, Giner RM, Recio MC (2012). Cucurbitacins as inducers of cell death and a rich source of potential anticancer compounds. Curr Pharm Des, 18, 1663-76. https://doi.org/10.2174/138161212799958549
  17. Rios JL, Escandell JM, Recio MC (2005). New insights into the bioactivity of cucurbitacins. In 'Studies in Natural Products Chemistry Volume 32: Bioactive Natural Products (Part L)', Eds Atta-ur-Rahman. Elsevier Science, pp 429-69.
  18. Seger C, Sturm S, Mair ME, Ellmerer EP, Stuppner H (2005a). 1H and 13C NMR signal assignment ofcucurbitacin derivatives fromCitrullus colocynthis (L.) Schrader and Ecballium elaterium L. (Cucurbitaceae). Magn Reson Chem, 43, 489-91. https://doi.org/10.1002/mrc.1570
  19. Seger C, Sturm S, Haslinger E, Stuppner H (2005b). NMR Signal assignment of 22-Deoxocucurbitacin D and cucurbitacin D from ecballium elaterium L. (Cucurbitaceae). Monatshefte fur Chemie, 136, 1645-49. https://doi.org/10.1007/s00706-005-0347-2
  20. Serpeloni JM, Specian AF, Ribeiro DL, et al (2015). Antimutagenicity and induction of antioxidant defense by flavonoid rich extract of Myrcia bella Cambess. in normal and tumor gastric cells. J Ethnopharmacol, 176, 345-55. https://doi.org/10.1016/j.jep.2015.11.003
  21. Sporn MB, Suh N (2000). Chemoprevention of cancer. Carcinogenesis, 21, 525-30. https://doi.org/10.1093/carcin/21.3.525
  22. Tan J, Qi H, Ni J (2015). Extracts of endophytic fungus xkc-s03 from Prunella vulgaris L. spica inhibit gastric cancer in vitro and in vivo. Oncol Lett, 9, 945-49. https://doi.org/10.3892/ol.2014.2722
  23. Torre LA, Bray F, Siegel RL, et al (2015). Global cancer statistics, 2012. CA Cancer J Clin, 65, 87-108. https://doi.org/10.3322/caac.21262
  24. Van Meerloo J, Kaspers GJ, Cloos J (2011). Cell sensitivity assays: the MTT assay. Methods Mol Biol, 731, 237-45.
  25. Velde VV, Lavie D (1983). 13C NMR spectroscopy of cucurbitacins. Tetrahedron, 39, 317-21. https://doi.org/10.1016/S0040-4020(01)91826-5
  26. Wei P, Zhiyu C, Xu T, Xiangwei Z (2015). Antitumor effect and apoptosis induction of Alocasia cucullata (Lour.) G. Don in human gastric cancer cells in vitro and in vivo. BMC Complement Altern Med, 15, 33. https://doi.org/10.1186/s12906-015-0554-2
  27. Zhang RL, Luo WD, Bi TN, Zhou SK (2012). Evaluation of antioxidant and immunity-enhancing activities of sargassum pallidum aqueous extract in gastric cancer rats. Molecules, 17, 8419-29. https://doi.org/10.3390/molecules17078419