Cytotoxic and Apoptotic Effects of Extracts of Artemisia ciniformis Krasch. & Popov ex Poljakov on K562 and HL-60 Cell Lines

  • Tayarani-Najaran, Zahra (Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences) ;
  • Hajian, Zahra (Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences) ;
  • Mojarrab, Mahdi (Novel Drug Delivery Research Center, School of Pharmacy, Kermanshah University of Medical Sciences) ;
  • Emami, Seyed Ahmad (Department of Pharmacognosy, School of Pharmacy, Mashhad University of Medical Sciences)
  • Published : 2014.09.15


Artemisia, as one of the largest genera in the tribe Anthemideae of the Asteraceae comprises an important part of Iranian flora. While cytotoxic and apoptotic properties have already been reported for some species of the genus there is not any report on cytotoxic effects of A. ciniformis. Petroleum ether (40-60), dichloromethane, ethyl acetate, ethanol and ethanol-water (50:50) extracts of the aerial parts of A. cinformis were subjected to cytotoxic and apoptotic evaluations on two cancer human cell lines (K562 and HL-60) and on J774 normal cells. Among multiple extracts evaluated for cytotoxicity, dichloromethane ($CH_2Cl_2$) and petroleum ether (PE) extracts were shown to possess the highest anti-proliferative effects on HL-60 and K562 cells with $IC_{50}$ values of 31.3 and $25.5{\mu}g/ml$ respectively. Apoptosis induction verified by sub-G1 peaks was seen in flow cytometry histograms. Increase in the amount of Bax protein, formation of DNA fragments, and cleavage of PARP to 24 and 89kDa sub units all confirmed induction of apoptosis by A. cinformis extracts. Taken together according to the result of the present study some extracts of A. cinformis could be considered as sources for natural cytotoxic compounds and further mechanistic and phytochemical studies are recommended to fully understand the underlying mechanisms of cnacer cell death as well as identification of responsible phytochemicals.


Artemisia ciniformis;asteraceae leukemic cell lines;petroleum ether extract;dichloromethane extract


Supported by : Mashhad University


  1. Abad MJ, Bedoya LM, Apaza L, et al (2012). The Artemisia L. genus, a review of bioactive essential oils. Molecules, 17, 2542-66.
  2. Aniya Y, Shimabukuro M, Shimoji M, et al (2000). Antioxidant and hepatoprotective actions of the medicinal herb Artemisia campestris from the Okinawa Islands. Biol Pharm Bull, 23, 309-12.
  3. Bora KS, Sharma A (2011). The genus Artemisia, a comprehensive review. Pharm Biol, 49, 101-9.
  4. Cerella C, Teiten MH, Radogna F, et al (2014). From nature to bedside, Pro-survival and cell death mechanisms as therapeutic targets in cancer treatment. Biotechnol Adv.
  5. Cha JD, Moon SE, Kim HY, et al (2009). Essential oil of Artemisia capillaris induces apoptosis in KB cells via mitochondrial stress and caspase activation mediated by MAPK-stimulated signaling pathway. J Food Sci, 74, 75-81.
  6. Colditz GA, Wei EK (2012). Preventability of cancer, the relative contributions of biologic and social and physical environmental determinants of cancer mortality. Annu Rev Public Health, 33, 137-56.
  7. Efferth T, Herrmann F, Tahrani A, et al (2011). Cytotoxic activity of secondary metabolites derived from Artemisia annua L. towards cancer cells in comparison to its designated active constituent artemisinin. Phytomed, 18, 959-69.
  8. Emami SA, Aghazari F. (2011). Les Phanerogames Endemiques de la Flore d'Iran. Teheran, Publications de I'Universite de Teheran,
  9. Emami SA, Taghizadeh Rabe SZ, Ahi A, et al (2012). Inhibitory activity of eleven Artemisia species from Iran against Leishmania major parasites. Iran J Basic Med Sci, 15, 807-11.
  10. Emami SA, Zamani Taghizadeh Rabe SH, Ahi A, et al (2010). Study on toxic effects of Artemisisa spp. fractions from Iran on human cancer cell lines. J Zanjan Univ Med Sci, 18, 58-67.
  11. Fasinu, Orisakwe (2013). Heavy metal pollution in sub-Saharan Africa and possible implications in cancer epidemiology. Asian Pac J Cancer Prev, 14, 3393-402.
  12. Firouzni A, Vahedi H, Sabbaghi F, et al (2008). Composition of the essential oil of Artemisia ciniformis, A. kopetdaghensis, and A. khorasanica in Iran. Chem Nat Compd, 44, 804-6.
  13. Ghahreman A, Attar F. (1999). Biodiversity of plant species in Iran. Tehran, Tehran University Publication.
  14. Gilani AH, Yaeesh S, Jamal Q, et al (2005). Hepatoprotective activity of aqueous-methanol extract of Artemisia vulgaris. Phytother Res, 19, 170-2.
  15. Jiang W, Huang Y, Wang JP, Yu XY, Zhang LY. (2013). The synergistic anticancer effect of artesunate combined with allicin in osteosarcoma cell line in vitro and in vivo. Asian Pac J Cancer Prev, 14, 4615-9.
  16. Judzentiene A, Budiene J, Gircyte R, et al (2012). Toxic activity and chemical composition of Lithuanian wormwood, et al (Artemisia absinthium L.)., essential oils. Rec Nat Prod, 6, 180-3.
  17. Kordali S, Cakir A, Mavi A, et al (2005a). Screening of chemical composition and antifungal and antioxidant activities of the essential oils from three Turkish Artemisia species. J Agric Food Chem, 53, 1408-16.
  18. Kordali S, Kotan R, Mavi A, et al (2005b). Determination of the chemical composition and antioxidant activity of the essential oil of Artemisia dracunculus and of the antifungal and antibacterial activities of Turkish Artemisia absinthium, A. dracunculus, Artemisia santonicum, and Artemisia spicigera essential oils. J Agric Food Chem, 53, 9452-8.
  19. Lee TK, Vairappan CS. (2011). Antioxidant, antibacterial and cytotoxic activities of essential oils and ethanol extracts of selected South East Asian herbs. J Med Plants Res, 5, 5284-90.
  20. Liu Y, Cui YF. (2013). Synergism of cytotoxicity effects of triptolide and artesunate combination treatment in pancreatic cancer cell lines. Asian Pac J Cancer Prev, 14, 5243-8.
  21. Mojarrab M, Jamshidi M, Ahmadi F, et al (2013). Extracts of Artemisia ciniformis protect cytotoxicity induced by hydrogen peroxide in H9c2 cardiac muscle cells through inhibition of reactive oxygen species. Adv Pharmacol Sci, Article ID 141683.
  22. Munker R, Marini F, Jiang S, et al (1997). Expression of CD95 (FAS), by gene transfer does not sensitize K562 to Faskilling. Hematol Cell Ther, 39, 75-8.
  23. Nicoletti I, Migliorati G, Pagliacci MC, et al (1991). A rapid and simple method for measuring thymocyte apoptosis by propidium iodide staining and flow cytometry. J Immunol Methods, 139, 271-9.
  24. O'Brien J, Wilson I, Orton T, et al (2000). Investigation of the Alamar Blue (resazurin), fluorescent dye for the assessment of mammalian cell cytotoxicity. Eur J Biochem, 267, 5421-6.
  25. Parsons MJ, Green DR. (2010). Mitochondria in cell death. Essays Biochem, 47, 99-114.
  26. Piao GC, Li YX, Yuan HD, et al (2012). Cytotoxic fraction from Artemisia sacrorum Ledeb. against three human cancer cell lines and separation and identification of its compounds. Nat Prod Res, 26, 1483-91.
  27. Rashid S, Rather MA, Shah WA, et al (2013). Chemical composition, antimicrobial, cytotoxic and antioxidant activities of the essential oil of Artemisia indica Willd. Food Chem, 138, 693-700.
  28. Renault TT, Manon S. (2011). Bax, addressed to kill. Biochimie, 93, 1379-91.
  29. Rustaiyan A, Masoudi S, Kazemi M. (2007). Volatile oils constituents from different parts of Artemisia ciniformis Krasch. et M. Pop. ex Poljak and Artemisia incana Druce. from Iran. J Essential Oil Res, 19, 548-51.
  30. Sehitoglu MH, Farooqi AA, Qureshi MZ, et al (2014). Anthocyanins: targeting of signaling networks in cancer cells. Asian Pac J Cancer Prev, 15, 2379-81.
  31. Singh NP, Ferreira JFS, Park JS, et al (2011). Cytotoxicity of ethanolic extracts of Artemisia annua to molt-4 human leukemia cells. Planta Med, 77, 1788-93.
  32. Spies L, Koekemoer TC, Sowemimo AA, et al (2013). Caspasedependent apoptosis is induced by Artemisia afra Jacq. ex Willd in a mitochondria-dependent manner after G2/M arrest. S Afr J Bot, 84, 104-9.
  33. Taghizadeh Rabe SZ, Mahmoudi M, Ahi A, et al (2011). Antiproliferative effects of extracts from Iranian Artemisia species on cancer cell lines. Pharm Biol, 49, 962-9.
  34. Tan RX, Tang HQ, Hu J, et al (1998). Lignans and sesquiterpene lactones from Artemisia sieversiana and Inula racemosa. Phytochemistry, 49, 157-61.
  35. Tayarani-Najaran Z, Sareban M, Gholami A, et al (2013). Cytotoxic and apoptotic effects of different extracts of Artemisia turanica Krasch. on K562 and HL-60 cell lines. Scientific World J, 2013, 628073.
  36. Tayarani-Najaran Z, Emami SA (2011). Cytotoxic Plants, Potential Uses in Prevention and Treatment of Cancer, Current Cancer Treatment-Novel Beyond Conventional Approaches, O. Ozdemir (editor), ISBN, 978-953-307-397-2, InTech.
  37. Tilaoui M, Mouse HA, Jaafari A, et al (2011). Chemical composition and antiproliferative activity of essential oil from aerial parts of a medicinal herb Artemisia herba-alba. Rev Bras Farmacogn, 21, 781-5.
  38. Wegiera M, Smolarz HD, Jedruch M, et al (2012). Cytotoxic effect of some medicinal plants from Asteraceae family on J-45.01 leukemic cell line-Pilot study. Acta Pol Pharm, 69, 263-8.