Nonapoptotic cell death induced by Hypericum species on cancer cells

Yıl 2017, Cilt: 3 Sayı: 1, 1 - 10, 04.03.2017

Ferda Ari Nazlihan Aztopal Merve Erkisa Serap Celikler Saliha Sahin Engin Ulukaya

https://doi.org/10.18621/eurj.292460

Öz

Objective. There are approximately 400 Hypericum species that grow naturally in different geographic origins of the world. Those species have been used in different folk medicines and screened for their biological activity including cancer. Our country is an important place for Hypericum species which are known as “kantaron, binbirdelik otu, kan otu, kılıç otu, yaraotu, kuzukıran”. We therefore evaluated the possible cytotoxic/apoptotic activities, total phenolic content and antioxidant capacity of the crude methanol extracts Hypericum adenotrichum Spach. and Hypericum olympicum L. which are still used in Turkish folk medicine. Methods. The total phenolic content and antioxidant capacity were determined by Folin-Ciocalteu and ABTS methods. Anti-growth effects were screened in human hepatoma (Hep3B) and rat glioma (C6) cell lines by the MTT and ATP viability assays. The cell death mode (apoptosis/necrosis) was investigated by fluorescence imaging and the level of caspase-cleaved cytokeratin 18 (M30), active caspase-3 and cleaved PARP (poly (ADP-ribose) polymerase). Results. The results indicate that the crude methanol extracts of Hypericum olympicum L. and Hypericum adenotrichum have both anti-growth/cytotoxic activities on these cells in a dose dependent manner. Conclusion. These extracts clearly induced non-apoptotic cell death in human hepatoma (Hep3B) and rat glioma (C6) cell lines. 

Anahtar Kelimeler

Hypericum olympicum, Hypericum adenotrichum, cell death, necrosis

Kaynakça

• [1] World Health Organization. The Global Burden of Disease, 2004; Update. Geneva: World Health Organization, 2008.
• [2] Song S, Xiong C, Zhou M, Lu W, Huang Q, Ku G, et al. Small-animal pet of tumor damage induced by photothermal ablation with 64 cu-bis-dota-hypericin. J Nucl Med 2011;52:792-9.
• [3] Cragg GM, Newman DJ. Plants as a source of anti-cancer agents. J Ethnopharmacol 2005;100:72-9.
• [4] Akerele O. Medicinal plants and primary health care: An agenda for action. Fitoterapia 1988;59:355-63.
• [5] Yazaki K, Okada T. Medicinal and aromatic plants VI. In: Bajaj YPS (ed.), Biotechnol Agric For Vol. 26, Springer-Verlag, Berlin, pp.167-78.
• [6] Demirci B, Baser KHC, Crockett S, Khan IA. Analyses of the volatile constituents of asian Hypericum L. species. J Essent Oil Res 2005;17:659-63.
• [7] Crockett SL, Robson NK. Taxonomy and chemotaxonomy of the genus Hypericum. Med Aromat Plant Sci Biotechnol 2011;5:1-13.
• [8] Hammer KD, Birt DF. Evidence for contributions of interactions of constituents to the anti-inflammatory activity of Hypericum perforatum. Crit Rev Food Sci Nutr 2014;54:781-9.
• [9] Peron AP, Mariucci RG, de Almeida IV, Dusman E, Mantovani MS, Vicentini VE. Evaluation of the cytotoxicity, mutagenicity and antimutagenicity of a natural antidepressant, hypericum perforatum l. (st. john's wort), on vegetal and animal test systems. BMC Complement Altern Med 2013;13:97.
• [10] Rouis Z, Abid N, Koudja S, Yangui T, Elaissi A, Cioni PL, et al. Evaluation of the cytotoxic effect and antibacterial, antifungal, and antiviral activities of Hypericum triquetrifolium turra essential oils from tunisia. BMC Complement Altern Med 2013;13:24.
• [11] Tala MF, Tchakam PD, Wabo HK, Talontsi FM, Tane P, Kuiate JR, et al. Chemical constituents, antimicrobial and cytotoxic activities of Hypericum riparium (Guttiferae). Rec Nat Prod 2013;7:65-8.
• [12] Rabanal RM, Bonkanka CX, Hernandez-Perez M, SanchezMateo CC. Analgesic and topical anti-inflammatory activity of Hypericum canariense L. and Hypericum glandulosum Ait. J Ethnopharmacol 2005;96:591-6.
• [13] Agostinis P, Vantieghem A, Merlevede W, de Witte PA. Hypericin in cancer treatment: more light on the way. Int J Biochem Cell Biol 2002;34:221-41.
• [14] Li XM, Luo XG, Ma N, Li K, Li W, Ma DY, et al. Quality and antitumour activity evaluation of extract of Hypericum ascyron. Biomed Chromatogr 2014;29:47-52.
• [15] Karioti A, Bilia AR. Hypericins as potential leads for new therapeutics. Int J Mol Sci 2010;11:562-94.
• [16] Schempp CM, Kiss J, Kirkin V, Averbeck M, Haarhaus BS, Kremer B, et al. Hyperforin acts as an angiogenesis inhibitor in vitro and in vivo. Planta Med 2005;71:999-1004.
• [17] Tchakam PD, Lunga PK, Kowa TK, Lonfouo AHN, Wabo HK, Tapondjou LA, et al. Antimicrobial and antioxidant activities of the extracts and compounds from the leaves of Psorospermum aurantiacum Engl. and Hypericum lanceolatum Lam. BMC Complement Altern Med 2012;12:136.
• [18] Dell AI, Caniato R, Biggin S, Garbisa S. Matrix proteases, green tea and St. John's wort: biomedical research catches up with folk medicine. Clin Chim Acta 2007;381:69-77.
• [19] Aztopal N, Erkisa M, Celikler S, Ulukaya E, Ari F. Antigrowth and apoptosis inducing effects of Hypericum olympicum L. and Hypericum adenotrichum Spach. on lung cancer cells in vitro: Involvement of DNA damage. J Food Biochem 2016;40:559-66.
• [20] Sarimahmut M, Balikci N, Celikler S, Ari F, Ulukaya E, Guleryuz G, et al. Evaluation of genotoxic and apoptotic potential of Hypericum adenotrichum Spach. in vitro. Regul Toxicol Pharmacol 2016;74:137-46.
• [21] Sahin S, Aybastier O, Isik E. Optimisation of ultrasonicassisted extraction of antioxidant compounds from Artemisia absinthium using response surface methodology. Food Chem 2013;141:1361-8.
• [22] Sahin S, Isik E, Aybastier O, Demir C. Orthogonal signal correction-based prediction of total antioxidant activity using partial least squares regression from chromatograms. J Chemom 2012;26:390-9.
• [23] van Meerloo J, Kaspers GJ, Cloos J. Cell sensitivity assays: the MTT assay. Methods Moll Biol 2011;731:237-45.
• [24] Andreotti PE, Cree IA, Kurbacher CM, Hartmann DM, Linder D, Harel G, et al. Chemosensitivity testing of human tumors using a microplate adenosine triphosphate luminescence assay: clinical correlation for cisplatin resistance of ovarian carcinoma. Cancer Res 1995;55:5276-82.
• [25] Ari F, Aztopal N, Icsel C, Yilmaz VT, Guney E, Buyukgungor O, et al. Synthesis, structural characterization and cell death-inducing effect of novel palladium (II) and platinum (II) saccharinate complexes with 2-(hydroxymethyl) pyridine and 2-(2-hydroxyethyl) pyridine on cancer cells in vitro. Bioorg Med Chem 2013;21:6427-34.
• [26] Siegel R, Naishadham D, Jemal A. Cancer statistics, 2013. CA Cancer J Clin 2013;63:11-30.
• [27] Mann J. Natural products in cancer chemotherapy: past, present and future. Nat Rev Cancer 2002;2:143-8.
• [28] Newman DJ, Cragg GM. Natural products as sources of new drugs over the 30 years from 1981 to 2010. J Nat Prod 2012;75:311-35.
• [29] Alipour BS, Ebrahimzadeh MA, Eslami B, Rahmani Z. Antıoxıdant activities of Hyperıcum fursei L. Latın Am Appl Res 2014;44:19.
• [30] Rainha N, Koci K, Coelho AV, Lima E, Baptista J, Fernandes-Ferreira M. HPLC-UV-ESI MS analysis of phenolic compound and antioxidant properties of Hypericum undulatum shootcultures and wild-growing plant Phytochemistry 2013;86:83-91.
• [31] Zorzetto C, Sanchez-Mateo CC, Rabanal RM, Lupidi G, Petrelli D, Vitali LA, et al. Phytochemical analysis and in vitro biological activity of three Hypericum species from the Canary Islands (Hypericum reflexum, Hypericum canariense and Hypericum grandifolium). Fitoterapia 2015;100:95-109.
• [32] Ramos AA, Marques F, Fernandes-Ferreira M, PereiraWilson C. Water extracts of tree Hypericum sps. protect DNA from oxidative and alkylating damage and enhance DNA repair in colon cells. Food Chem Toxicol 2013;51:80-6.
• [33] Zeng JZ, Sun DF, Wang L, Cao X, Qi JB, Yang T, et al. Hypericum sampsonii induces apoptosis and nuclear export of retinoid X receptor-alpha. Carcinogenesis 2006;27:1991-2000.
• [34] Martarelli D, Martarelli B, Pediconi D, Nabissi MI, Perfumi M, Pompei P. Hypericum perforatum methanolic extract inhibits growth of human prostatic carcinoma cell line orthotopically implanted in nude mice. Cancer Lett 2004;210:27-33.
• [35] Cirak C, Ivanauskas L, Janulis V, Radusiene J. Chemical constituents of Hypericum adenotrichum Spach, an endemic Turkish species. Nat Prod Res 2009;23:1189-95.
• [36] Cirak C, Radusiene J, Camas N, Caliskan O, Odabas MS. Changes in the contents of main secondary metabolites in two Turkish Hypericum species during plant development. Pharm Biol 2013;51:391-9.
• [37] Sackova V, Kulikova L, Kello M, Uhrinova I, Fedorocko P. Enhanced antiproliferative and apoptotic response of HT-29 adenocarcinoma cells to combination of photoactivated hypericin and farnesyltransferase inhibitor manumycin A. Int J Mol Sci 2011;12:388-405.
• [38] Billard C, Merhi F, Bauvois B. Mechanistic insights into the antileukemic activity of hyperforin. Curr Cancer Drug Targets 2013;13:1-10.
• [39] Ozmen A, Bauer S, Gridling M, Singhuber J, Krasteva S, Madlener S, et al. In vitro anti-neoplastic activity of the ethnopharmaceutical plant Hypericum adenotrichum Spach endemic to Western Turkey. Oncol Rep 2009;22:845-52.