Artichoke compound cynarin differentially affects the survival, growth, and stress response of normal, immortalized, and cancerous human cells

Cynarin (CYN) is the main derivative of caffeoylquinic acid, found in leaves and heads of artichoke. It may have hepatoprotective, antiatherosclerotic, antioxidative, choleretic, and cholesterol-lowering effects. We tested the effects of various doses of CYN on the proliferative potential, survival, morphology, and stress response (SR) markers heme oxygenase-1 (HO-1) and heat shock protein-70 (HSP70) in normal human skin fibroblasts (FSF-1), telomerase-immortalized mesenchymal stem cells (hTERT-MSC), and cervical cancer cells (HeLa). The effects of CYN on cell proliferation and morphology were dose- and cell type-dependent, with 500 µM CYN as the upper limit for all cell types. While the growth and proliferation of cells decreased after exposure to 75 µM CYN for 3 days, overall survival of FSF-1 and hTERT-MSC was higher than that of HeLa cells. Furthermore, CYN induced the oxidative SR marker HO-1 in both fibroblasts and stem cells in a biphasic manner. A slight induction of HSP70 was observed only in the stem cells. Thus, CYN may be useful for protection against the growth and survival of potentially cancerous cells and may promote longevity of normal cells by inducing SR proteins. Further advanced research related to CYN and artichoke is recommended.

Artichoke compound cynarin differentially affects the survival, growth, and stress response of normal, immortalized, and cancerous human cells

Cynarin (CYN) is the main derivative of caffeoylquinic acid, found in leaves and heads of artichoke. It may have hepatoprotective, antiatherosclerotic, antioxidative, choleretic, and cholesterol-lowering effects. We tested the effects of various doses of CYN on the proliferative potential, survival, morphology, and stress response (SR) markers heme oxygenase-1 (HO-1) and heat shock protein-70 (HSP70) in normal human skin fibroblasts (FSF-1), telomerase-immortalized mesenchymal stem cells (hTERT-MSC), and cervical cancer cells (HeLa). The effects of CYN on cell proliferation and morphology were dose- and cell type-dependent, with 500 µM CYN as the upper limit for all cell types. While the growth and proliferation of cells decreased after exposure to 75 µM CYN for 3 days, overall survival of FSF-1 and hTERT-MSC was higher than that of HeLa cells. Furthermore, CYN induced the oxidative SR marker HO-1 in both fibroblasts and stem cells in a biphasic manner. A slight induction of HSP70 was observed only in the stem cells. Thus, CYN may be useful for protection against the growth and survival of potentially cancerous cells and may promote longevity of normal cells by inducing SR proteins. Further advanced research related to CYN and artichoke is recommended.

___

  • Adzet T, Puigmacia M (1985). High-performance liquid chromatography of caffeoylquinic acid derivatives of Cynara scolymus L. leaves. J Chromatogr 348: 447–453.
  • Alonso MR, García MC, Bonell CG, Ferraro G, Rubio M (2006). Validated HPLC method for cynarin determination in biological samples. Acta Farm Bonaerense 25: 267–270.
  • Argyopoulou A, Aligiannis N, Trougakos IP, Skaltsounis AL (2013). Natural compounds with anti-ageing activity. Nat Prod Rep 30: 1412–1437.
  • Atasever B, Akgün DK, Kuruca S, Turan N, Seyhanli V, Meriçli A (2003). Effects of flavonoids obtained from Cynara syriaca on leukemic cells. J Fac Pharm Ankara 32: 143–150.
  • Balogun E, Hoque M, Gong P, Killeen E, Green CJ, Foresti R, Alam J, Motterlini R (2003). Curcumin activates the haem oxygenase-1 gene via regulation of Nrf2 and the antioxidant responsive element. Biochem J 371: 887–895.
  • Barnes J, Anderson LA, Phillipson JD (2007). Herbal Medicines. 3rd ed. London, UK: Pharmaceutical Press.
  • Chen CY, Yang JH, Li MH, Surh YJ (2005). Resveratrol upregulates heme oxygenase-1 expression via activation of NF-E2-related factor 2 in PC12 cells. Biochem Bioph Res Co 331: 993–1000.
  • Demirovic D, Rattan SIS (2011). Curcumin induces stress response and hormetically modulates wound healing ability of human skin fibroblasts undergoing ageing in vitro. Biogerontology 12: 437–444.
  • Dong GC, Chuang PH, Chang K, Jan P, Hwang PI, Wu HB, Yi M, Zhou HX, Chen HM (2009). Blocking effect of an immuno- suppressive agent, cynarin, on CD28 of T cell receptor. Pharmaceut Res 26: 375–381.
  • Dunsmore K, Chen PG, Wong HR (2001). Curcumin, a medicinal herbal compound capable of inducing the heat shock response. Crit Care Med 29: 2199–2204.
  • Ebadi M (2007). Pharmacodynamic Basis of Herbal Medicine. 2nd ed. Boca Raton, FL, USA: CRC Press.
  • Ernst E, Pittler MH (2000). Safety issues in phytotherapy. In: Ernest E, editor. Herbal Medicine: A Concise Overview for Professionals. 1st ed. Oxford, UK: Butterworth-Heinemann, pp. 82–100.
  • Gouveia SC, Castilho PC (2012). Phenolic composition and antioxidant capacity of cultivated artichoke, Madeira cardoon and artichoke‐based dietary supplements. Food Res Int 48: 712–724.
  • Hayes DP (2007). Nutritional hormesis. Eur J Clin Nutr 61: 147–159.
  • Jİrgensen P, Milkovic L, Zarkovic N, Waeg G, Rattan SIS (2014). Lipid peroxidation-derived 4-hydroxynonenal-modiŞed proteins accumulate in human facial skin Şbroblasts during ageing in vitro. Biogerontology 15: 105–110.
  • Juan SH, Cheng TH, Lin HC, Chu YL, Lee WS (2005). Mechanism of concentration-dependent induction of heme oxygenase-1 by resveratrol in human aortic smooth muscle cells. Biochem Pharmacol 69: 41–48.
  • Kasımoğulları SÇ, Oran S, Arı F, Ulukaya E, Aztopal N, Sarımahmut M, Öztürk Ş (2014). Genotoxic, cytotoxic, and apoptotic effects of crude extract of Usnea filipendula Stirt. in vitro. Turk J Biol 38: 940-947.
  • Lattanzio V, Kroon PA, Linsalata V, Cardinali A (2009). Globe artichoke: a functional food and source of nutraceutical ingredients. J Funct Foods 1: 131–144.
  • Lee J, Jo DG, Park D, Chung HY, Mattson MP (2014). Adaptive cellular stress pathways as therapeutic targets of dietary phytochemicals: focus on the nervous system. Pharmacol Rev 66: 815–868.
  • Lucey BP, Rees WAN, Hutchins GM (2009). Henrietta Lacks, HeLa cells, and cell culture contamination. Arch  Pathol  Lab Med 133: 1463–1467.
  • Mattson MP (2008). Dietary factors, hormesis, and health. Ageing Res Rev 7: 43–48.
  • Negro D, Montesano V, Grieco S, Crupi P, Sarli G, De Lisi A, Sonnante G (2012). Polyphenol compounds in artichoke plant tissues and varieties. J Food Sci 77: 244–252.
  • Özkan A, Erdoğan A (2013). Membrane and DNA damaging/ protective effects of eugenol, eucalyptol, terpinen-4-ol, and camphor at various concentrations on parental and drug- resistant H1299 cells. Turk J Biol 37: 405–413.
  • Pullikotil P, Chen H, Muniyappa R, Greenberg CC, Yang S, Reiter CEN, Lee JW, Chung JH, Quon MJ (2012). Epigallocatechin gallate induces expression of heme oxygenase-1 in endothelial cells via p38 MAPK and Nrf-2 that suppresses pro-inflammatory actions of TNF-α. J Nutr Biochem 23: 1134–1145.
  • Putics A, Végh EM, Csermely P, Soti C (2008). Resveratrol induces the heat-shock response and protects human cells from severe heat stress. Antioxid Redox Sign 10: 65–75.
  • Rattan SIS (2005). Hormetic modulation of ageing and longevity by mild heat stress. Dose-Response 3: 533–546.
  • Rattan SIS (2008). Hormesis in aging. Ageing Res Rev 7: 63–78.
  • Rattan SIS (2013). Nutritional hormetins and ageing. In: Watson RR and Preedy VR, editors. Bioactive Food as Dietary Interventions for Ageing Population. 1st ed. London, UK: Academic Press, pp. 205.
  • Rattan SIS, Ali RE (2007). Hormetic prevention of molecular damage during cellular aging of human skin fibroblasts and keratinocytes. Ann NY Acad Sci 1100: 424–430.
  • Rattan SIS, Fernandes RA, Demirovic D, Dymek B, Lima CF (2009). Heat stress and hormetin-induced hormesis in human cells: effects on aging, wound healing, angiogenesis, and differentiation. Dose-Response 7: 90–103.
  • Rattan SIS, Kryzh V, Schnebert S, Perrier E, Nizard C (2013). Hormesis based anti-ageing products: a case study of novel hormetics. Dose-Response 11: 99–108.
  • Scapagnini G, Foresti R, Calabrese V, Stella AMG, Green CJ, Motterlini R (2002). Caffeic acid phenethyl ester and curcumin: a novel class of heme oxygenase-1 inducers. Mol Pharmacol 3: 554–561.
  • Simonsen JL, Rosada C, Serakinci N, Justesen J, Stenderup K, Rattan SIS, Jensen TG, Kassem M (2002). Telomerase expression extends the proliferative life-span and maintains the osteogenic potential of human bone marrow stromal cells. Nat Biotechnol 20: 592–596.
  • Slanina J, Taborska E, Bochorakova H, Slaninova I, Humpa O, Robinson WE, Schram KH (2001). New and facile method of preparation of the anti-HIV-1 agent, 1,3-dicaffeoylquinic acid. Tetrahedron Lett 42: 3383–3385.
  • Son TG, Camandola S, Mattson MP (2008). Hormetic dietary phytochemicals. Neuromol Med 10: 236–246.
  • Wu CC, Hsu MC, Hsieh CW, Lin JB, Lai PH, Wung BS (2006). Upregulation of heme oxygenase-1 by epigallocatechin-3-gallate via the phosphatidylinositol 3-kinase/Akt and ERK pathways. Life Sci 78: 2889–2897.
Turkish Journal of Biology-Cover
  • ISSN: 1300-0152
  • Yayın Aralığı: Yılda 6 Sayı
  • Yayıncı: TÜBİTAK
Sayıdaki Diğer Makaleler

Enhancing the expression of Aspergillus niger ß-mannanase in Pichia pastoris by coexpression of protein disulfide isomerase

XIAOLING CHEN, BO ZHOU, MENG XU, ZHIQING HUANG, GANG JIA, JIAYUN QIAO, GUANGMANG LIU

Two-dimensional gel-based serum protein profile of growing piglets

MALGORZATA OZGO, ADAM LEPCZYNSKI, AGNIESZKA HEROSIMCZYK

Micropropagation of Vaccinium myrtillus L. (Bilberry) naturally growing in the Turkish flora

MUSTAFA CÜCE, ATALAY SÖKMEN

Salicylic acid alleviates cold-induced photosynthesis inhibition and oxidative stress in Jasminum sambac

HAN CAI, MENGYING HE, KUN MA, YONGGAO HUANG, YUN WANG

Effects of Turkish propolis extract on secretion of polymorphonuclear elastase following respiratory burst

YAŞAM BARLAK, ORHAN DEĞER, MELTEM UÇAR, TUĞBA NİGAR ÇAKIROĞLU

Micropropagation of Vaccinium myrtillus L. (Bilberry) naturally growing in the Turkish fora

Atalay SÖKMEN, Mustafa CÜCE

Energy effciency of the sunlight harvesting and storing system in bacterial photosynthesis: comparison with semiconductor photovoltaic cells

Abdurasul YARBEKOV, Mavluda ZAKHIDOVA, Vakhobjon KUVONDIKOV, Erkin NORMATOV, Aziz SAPARBAYEV, Erkin ZAKHIDOV, Abdumutallib KOKHKHAROV, Sherzod NEMATOV

Energy efficiency of the sunlight harvesting and storing system in bacterial photosynthesis: comparison with semiconductor photovoltaic cells

ERKIN ZAKHIDOV, MAVLUDA ZAKHIDOVA, ABDUMUTALLIB KOKHKHAROV, ABDURASUL YARBEKOV, VAKHOBJON KUVONDIKOV, SHERZOD NEMATOV, ERKIN NORMATOV, AZIZ SAPARBAYEV

Purifcation and characterization of a cyanide-degrading nitrilase from Trichoderma harzianum VSL291

Jorge RODRIGUE RICANO, Mario RAMIREZ LEPE

Enhancing the expression of Aspergillus niger β-mannanase in Pichia pastoris by coexpression of protein disulfde isomerase

Bo ZHOU, Meng XU, Xiaoling CHEN, Zhiqing HUANG, Gang JIA, Jiayun QIAO, Guangmang LIU