In vitro Investigation of Cytotoxic and Apoptotic Effects of Cynara L. Species in Colorectal Cancer Cells

  • Simsek, Ela Nur (Department of Biology, Science Faculty, Selcuk University) ;
  • Uysal, Tuna (Department of Biology, Science Faculty, Selcuk University)
  • Published : 2013.11.30


Apoptotic and cytotoxic activity of plant extracts obtaining from naturally growing Cynara syriaca in Turkey and cultivated C cardunculus against DLD1 colorectal cancer cells was determined. Extracts from wild and cultivated Cynara species were obtained from their vegetative parts and receptacles using hexane and applied with five different dose (0.1-1 mg/ml) as well as apigenin for MTT tests for three time periods (24, 48 and 72 hours). After cells were treated with $IC_{50}$ doses for each extract total DNA and RNA were isolated for determination of the cause of cell death. From isolated RNAs, cDNA were synthesized and amplification of p21, BCL-2 and BAX gene regions was carried out. Consequently, we found that pro-apoptotic (BAX) gene expression and a cell cycle inhibitor (p21) were induced in the presence of our artichoke extracts. In contrast, anti-apoptotic BCL-2 gene expression was reduced compared to the control group. In addition DNA fragmentation results demonstrated DLD1 cell death via apoptosis.


Artichoke;cDNA;colorectal cancer;DLD1;DNA fragmentation;anti-cancer agent


  1. Adzet T, Camarasa J, Carlos Laguna J (1987). Hepatoprotective activity of polyphenolic compounds from Cynara scolymus against CCl4 toxicity in isolated rat hepatocytes. J Natural Products. 50, 612-7.
  2. Chresta CM, Masters JRW, Hickman JA (1996). Hypersensitivity of human testicular tumors to etoposide-induced apoptosis is associated with p53 and high Bax: Bcl-2 ratio. Cancer Res, 56, 1834-41.
  3. Chowdhury AR, Sharma S, Mandal S, et al (2002). Luteolin, an emerging anti-cancer flavonoid, poisons eukaryotic DNA topoisomerase I. Biochem J, 366, 653-61.
  4. Conforti F, Ioele G, Statti GA, et al (2008). Antiproliferative activity against human tumor cell lines and toxicity test on Mediterranean dietary plants. Food Chem Toxicol, 46, 3325-32.
  5. Eliopoulos AG, Kerr DJ, Herod J, et al (1995). The control of apoptosis and drug resistance in ovarian cancer: influence of p53 and Bcl-2. Oncogene, 111217-28.
  6. Elmore S (2007). Apoptosis: A review of programmed cell death. Toxicol. Pathol, 35, 495-516.
  7. Gebhardt R (1997). Antioxidative and protective properties of extracts from leaves of the artichoke (Cynara scolymus L.) against hydroperoxide-induced oxidative stress in cultured rat hepatocytes. Toxicology and Applied Pharmacology, 144, 279-86.
  8. Gebhardt R (1998). Inhibition of cholesterol biosynthesis in primary cultured rat hepatocytes by artichoke (Cynara scolymus L.) extracts. J Pharmacol Exp Ther, 286, 1122-8.
  9. Greenwald P, Clifford CK, Milner JA (2001). Diet and cancer prevention. Eur J Cancer, 37, 948-65.
  10. Janicke RU, Sprengart ML, Wati MR, et al (1998). Caspase-3 is required for DNA fragmentation and morphological changes associated with apoptosis. J Biol Chem, 273, 9357-60.
  11. Jimenez-Escrig A, Dragsted LO, Daneshvar B, et al (2003). In vitro antioxidant activities of edible artichoke (Cynara scolymus L.) and effect on biomarkers of antioxidants in rats. J Agric Food Chem. 51, 5540-5.
  12. Juzyszyn Z, Czerny B, Mysliwiec Z, et al (2010). The effect of artichoke (Cynara scolymus L.) extract on respiratory chain system activity in rat liver mitochondria. Phytother Res, 24, 123-8.
  13. Liu LZ, Fang J, Zhou Q, et al (2005). Apigenin inhibits expression of vascular endothelial growth factor and angiogenesis in human lung cancer cells: implication of chemoprevention of lung cancer. Mol Pharmacol, 68, 635-43.
  14. Lupattelli G, Marchesi S, Lombardini R, et al (2004). Artichoke juice improves endothelial function in hyperlipemia. Life Sci, 76, 775-82.
  15. Menghini L, Genovese S, Epifano F, et al (2010). Antiproliferative, protective and antioxidant effects of artichoke, dandelion, turmeric and rosemary extracts and their formulation. Int J Immunopathol Pharmacol, 23, 601-10.
  16. Miccadei S, Di Venere D, Cardinali A, et al (2008). Antioxidative and apoptotic properties of polyphenolic extracts from edible part of artichoke (Cynara scolymus L.) on cultured rat hepatocytes and on human hepatoma cells. Nutr Cancer, 60, 276-83.
  17. Mileo AM, Di Venere D, Linsalata V (2012). Artichoke polyphenols induce apoptosis and decrease the invasive potential of the human breast cancer cell line MDA-MB231. J Cell Physiol, 227, 3301-9.
  18. Mosmann T (1983). Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods, 65, 55-63.
  19. Nadova S, Miadokova E, Mucaji P, Grancai D, Cipak L, (2008). Growth inhibitory effect of ethyl acetate-soluble fraction of Cynara cardunculus L. in leukemia cells involves cell cycle arrest, cytochrome c release and activation of caspases. Phytother Res, 22, 165-8.
  20. Oltvai ZN, Milliman CL, Korsmeyer SJ (1993). Bcl-2 heterodimerizes in vivo with a conserved homology, Bax, that accelerates programmed cell death. Cell, 74, 609-19.
  21. Saenz Rodreguez T, Garcia Gimenez D, de la Puerta Vazquez R, (2002). Choleretic activity and biliary elimination of lipids and bile acids induced by an artichole leaf extract in rats. Phytomedicine, 9, 8.
  22. Salomons GS, Brady HJ, Verwijs-Janssen M, et al (1997). The Bax alpha: Bcl-2 ratio modulates the response to dexamethasone in leukaemic cells and is highly variable in childhood acute leukaemia. Int J Cancer, 71, 959-65.<959::AID-IJC9>3.0.CO;2-X
  23. Saraste A, Pulkki K (2000). Morphologic and biochemical hallmarks of apoptosis. Cardiovasc Res, 45, 528-37.
  24. Speroni E, Cervetallati R, Govoni P, et al (2003). Efficacy of different Cynara scolymus preparations on liver complaints. J Ethnopharmacol, 86, 203-11.
  25. Tallman MS, Gilliland DG, Rowe JM (2005). Drug therapy for acute myeloid leukemia. Blood, 106, 1154-63.
  26. Wang M, Simon JE, Aviles IF, et al (2003). Analysis of antioxidative phenolic compounds in artichoke (Cynara scolymus L.). J Agric Food Chem, 51, 601-8.
  27. Wegener T, Fintelmann V (1999). Pharmacological properties and therapeutic profile of artichoke (Cynara scolymus L.). Wien Med Wochenschr, 149, 241-7.
  28. Yang Huang W, Zhong Cai Y, Zhang Y (2009). Natural phenolic compounds from medicinal herbs and dietary plants: potential use for cancer prevention. Nutrition and Cancer, 62, 1-20.

Cited by

  1. Establishment and Partial Characterization of an Epirubicin-Resistant Gastric Cancer Cell Line with Upregulated ABCB1 vol.15, pp.16, 2014,
  2. Expression of miR-711 and mechanism of proliferation and apoptosis in human gastric carcinoma vol.14, pp.4, 2017,