Liken sekonder bileşiklerinin farklı insan kanser hücre tipleri üzerine antikanserojenik etkisi

Günümüzde kanser henüz çözümlenememiş önemli bir sağlık problemidir. Kanser tedavisinde temel olarak cerrahi, kemoterapi ve hormon tedavi yöntemleri kullanılmaktadır. Kanser tedavisinde kullanılan bu temel yöntemlerin ve ilaçların tedavide yetersiz olduğu düşünülmektedir. Bu tedavi yöntemleri bazı yan etkilere sahiptir ve tedaviler uzun sürmektedir. Son yıllarda kanser tedavisinde karşılaşılan sorunlar nedeniyle alternatif tedavi yöntemleri aranmaktadır. Bu amaç doğrultusunda son zamanlarda yapılan çalışmalarda çeşitli kanser tiplerine karşı sentetik, bitkisel ve fungus kaynaklı ilaçların antikanser etkileri araştırılmaya başlanmıştır. Yapılan bu araştırmalar sonucunda likenler ve sekonder metabolitlerinin de kanser tedavisinde çözüm olabilmesi için alternatif bir yöntem olarak kullanılması önerilmiştir. Likenler; mantarların alglerle bir araya gelerek meydana getirdikleri morfolojik ve fizyolojik birlikler olarak tanımlanmaktadır. Bu metabolitler yağlı asitler ve laktonlar, zeorin grubu bileşikler, pulvik asit türevleri, kumaron türevleri, depsidler, depsidonlar ve antrokinon türevleri olarak sınıflandıralabilirler. Son beş yıldır liken sekonder metabolitlerinin farklı kanser hücre tipleri üzerinde yapılan çalışmaları umut vericidir; ilaç aday molekülü bulmayı hedeflemektedir.

Evaluation of the impact on different types of human cancer cell of lichen secondary compounds

Today, cancer is appearing as a major unsolved health problem. Basicly, surgery, chemotherapy and hormone therapy models are used in the treatment of cancer. Basic procedures and drugs used in the treatment of cancer are thought to be insufficient. These treatments have some side effects and they take a long time. Due to the problems encountered in the treatment of cancer in the recent years, alternative methods of treatment are being researched. For this purpose the effect of herbal, synthetic and fungus organisms against various types of cancer is being investigated. As a result of these investigations, lichens and their secondary metabolites are also proposed to be used as an alternative method in cancer treatment. Lichens are a symbiotic association of a fungus and a photosynthetic partner. These metabolites were identified as fatty acids, lactons, zeorin, pulvic acid, petroleum, depsids, depsidons and antrokinon derivatives. Impact of lichen secondary compound studies on different human cancer types, aims to find a promising drug Candidate molecule.

___

  • 1. Merlo LM, Pepper JW, Reid BJ, Carlo C. Maley Cancer as an evolutionary and ecological process. Nat Rev Cancer, 2006; 6: 924-35.
  • 2. Nowell PC. The clonal evolution of tumor cell populations. Science, 1976; 194: 23-8.
  • 3. Guyton AC, Hall JE. Protein sentezi, hücre fonksiyonu ve hücre çoğalmasının genetik kontrolü. In: Çavuşcuoğlu H, eds. Tıbbi Fizyoloji. 10th ed. Ankara: Nobel Tıp Kitapevleri Ltd Şti, 2001: 24-37.
  • 4. Klug WS, Cummings MR, Spencer CA. Hücre döngüsünün düzenlenmesi ve kanser. In: Öner C, Sümer S, Öner R, Öğüş A, Açık L. Genetik Kavramlar. 8th ed. Ankara: Palme Yayıncılık, 2011: 434-56.
  • 5. Herceg Z and Hainaut P. Genetic and epigenetic alterations as biomarkers for cancer detection, diagnosis and prognosis. Mol Oncol, 2007; 1: 26-41.
  • 6. Anonim. Kanser Biyolojisini Anlamak. http:// www.stoma-seite.de/SiklusApoptozisKanser.pdf (Erişim tarihi : 17.07.2013)
  • 7.Öktem S, Özhan MH, Özol D. Apoptozisin Önemi. Toraks Derg, 2001; 2(1): 91-5.
  • 8. Lowitz BB, Casciato DA. Manual of Clinical Oncolog. Lippincott, Williams and Wilkins, 2000.
  • 9.World2008. Health Organization.World Cancer Report.
  • 10. Anonim. Kanser nedir? www.cancervic.org.au/ cancer1/multilingualInformation/pdfs/turkish/ CancerWhatIs.pdf (Erişim tarihi : 17.07.2013)
  • Türkiye İstatistik Kurumu (TÜİK). Türkiye İstatistik Yıllığı. 2011.
  • Anonim. Sağlıklı Bilgiler-30: Meme Kanseri, www. mesahastanesi.com.tr (Erişim tarihi : 17.07.2013)
  • Anonim. Kanser, http://tr.wikipedia.org/wiki/ Kanser (Erişim tarihi : 17.07.2013)
  • Mork CN, Faller DV, Spanjaard RA. Loss of putative tumor suppressor EI24/PIG8 confers resistance to etoposide. FEBS Letters, 2007; 581:5440-4.
  • 15.Vetoshkina TV, Dubskaya TY, Fomina TI, Ermolaeva LA, Goldberg VE. Toxic effect of vepesid on morphology and function of the rat liver. Bull Exp Biol Med, 2007; 143: 21-3.
  • 16.Borovskaya TG, Goldberg VE, Shchemerova YA, Perova AV, Timina EA, Pakhomova AV. Evaluation of the progeny of rats treated with topoisomerase II inhibitor vepesid. Bull Exp Biol Med, 2006; 141(5): 515-8.
  • 17. Korkmaz S. Paklitaksel, Kersetin ve Berberinin, A549, HeLa, HT-29, MCF-7 veNIH3T3 Hücre Kültürlerinde Sitotoksik Etkilerinin Değerlendirilmesi. Anadolu Üniversitesi Sağlık Bilimleri Enstitüsü, Doktora Tezi, 2002.
  • 18. Turan N. Nerium oleander Bitkisinin, Kök, Yaprak ve Gövde Ekstrelerinin Lösemi Hücrelerine Sitotoksik Etkileri, Yüksek Lisans Tezi, İstanbul Üniversitesi, Fen Bilimleri Enstitüsü, 2003.
  • 19. Lee K. Anticancer drug design based on plant- derived natural products, J Biomed Sci, 1999; 6: 236-50.
  • 20. El-Shazly MM, El-Zayat EM, Hermersdörfer H. Insecticidal activity, mammalian cytotoxicity and mutagenicity of an ethanolic extract from Nerium oleander (Apocynaceae), Ann Appl Biol, 2000; 136: 153-57.
  • 21. Zhao Q, Li B, Weber N, Lou Y, Proksch P. Estrogen- like effects of ethanol extracts from several Chinese legumes on MCF-7 cell. Europ Food Res Tech, 2005; 221: 828-33.
  • 22. Stagos D, Gregorios DA, Antonios M, Spyrou A, Tsatsakis AM, Kouretas D. Chemoprevention of liver cancer by plant polyphenols. Food Chem Toxicol, 2012; 50(6): 2155-70.
  • 23. Kitdamrongtham W, Manosroi A, Akazawa H, Gidado A, Stienrut P, Manosroi W et al. Potent anti-cervical cancer activity: Synergistic effects of Thai medicinal plant in recipe N040 selected from the MANOSROI III database. J Ethnopharm, 2013; 149(1): 288-96.
  • 24. Ziech D, Anestopoulos I, Hanafi R, Voulgaridou GP, Franco R, Georgakilas AG et al. Pleiotrophic effects of natural products in ROS-induced carcinogenesis: The role of plant-derived natural products in oral cancer chemoprevention. Cancer Lett, 2012; 327(1-2): 16-25.
  • 25.Hostanska K, Nisslein T, Freudenstein J, Reichling J, Saller R. Cimicifuga racemosa extract inhibits proliferation of estrogen receptor- positive and negative human breast carcinoma cell lines by induction of apoptosis. Breast Cancer Res Treat, 2004; 84: 151-60.
  • 26.Einbond LS, Shimizu M, Xiao D, Nuntanakorn P, Lim JTE, Suzui M, et. al. Growth inhibitory activity of extracts and purified components of black cohosh on human breast cancer cells. Breast Cancer Res Treat, 2004; 83: 221-31.
  • 27.Sharma G, Tyagi KA, Singh RP, Chan DCF, Agarwall R. Synergistic anticancer effects of grape seed extract and conventional cytotoxic agent doxorubicin against human breast cancer cells. Breast Cancer Res Treat, 2004; 85: 1-12.
  • 28. Afag F, Saleem M, Aziz MH, Mukhtar H. Inhibition of 12 otetradecanoylphorbol- 13-acetate-induced tumor promotion markers in CD-1 mouse skin by olenadrin. Toxicol App Pharmacol, 2004; 195: 361-69.
  • 29.Sreenivasan Y, Rafhavendra PB, Manna SK. Oleandrin- Mediated expression of fas potentiates apoptosis in tumor cells. J Clin Immun, 2006; 26 (4): 308-10.
  • 30.Smith JA, Madden T, Vijjswarapu M, Newman RA. Inhibition of export of fibroblast growth factor 2 (FGF-2) from the prostate cancer cell lines PC3 and DU145 by anvirzel and its cardiac glycoside component, oleandrin. Biochem Pharmocol, 2001; 62: 469-72.
  • 31. Erdemoğlu N, Küpeli E, Yeşilada E. Antiimflammatory and antinociceptive activity assessment of plants used as remedy in Turkish folk medicine. J Ethnopharm, 2003; 89: 123-9.
  • 32. Sreenivasan Y, Sarkar A, Manna SK. Oleandrin suppresses activation of nuclear transcription factor-kB and activator protein 1 and potentiates apoptosis induced by ceramide. Biochem Pharmacol, 2003; 66: 2223-39.
  • 33. Mc Conkey DJ, Lin Y, Nutt LK, Ozel HZ, Newman RA. Cardiac glycosides stimulate Ca+2 increases and apoptosis in androgen independent, Metastatic human prostate adenocarcinoma cells. Cancer Res, 2000; 60 (14): 3807-12.
  • 34. Gozum S, Tezel A, Koc M. Complementary alternative treatments used by patients with cancer in eastern Turkey. Cancer Nurs, 2003; 26: 230-6.
  • 35. World Health Organization Geneva. WHO 2002- 2005. Traditional Medicine Strategy. 29-74.
  • 36. El-Ansari M.A.El, Nawwar MA, Saleh NA. Stachysetin, adiapigenine-7- glucosidep-p- dihydroxy-truxinate from Stachys Aegyptiaca. Phytochem, 1995; 40: 1543–8.
  • 37.Paternostro MP, Maggio AM, Piozzi F, Servettaz O. Labdane diterpenes from Stachys plumosa. J Nat Produc, 2000; 63: 1166–7.
  • 38. Fazio C, Passannanti S, Paternostro MP. Arnold NA. Diterpenoids from Stachys mucronata. Planta Med, 1994; 60: 499.
  • 39. Nishimura H, Sasaki H, Inagaki N, Chin M, Mitsuhashi H. Nine phenethyl alcohol glycosides from Stachys seiboldii. Phytochem, 1991; 30: 965–9.
  • 40. Miyase T, Yamamoto R, Ueno, A. Phenyl ethanoid glycosides from Stachys officinalis. Phytochem, 1996; 43: 475–9.
  • 41.Yamamoto R, Miyase T, Ueno A. Stachys saponins I–VIII, new oleananetype triterpene saponins from Stachys riederi Chamisso. Chem Pharmacol Bull, 1994; 42: 1291–6.
  • 42.Hayashi K, Nagamatsu T, Ito M, Hattori T, Suzuki Y. Acotoside, a component of Stachys sieboldii MIQ, may be a promising antinephritic agent. Effects of acetoside on crescentic-type anti-GBM nephritis in rats. Japan J Pharmacol, 1994; 65: 143–51.
  • 43. Skaltsa HD, Bermejo P, Lazari DM, Silvan AM, Skaltsounis AL, Sanz A et. al. Inhibition of prostaglandin E2 and leukotriene C4 in Mouse peritoneal macrophages and thromboxan B2 production in human platelets by flavonoids from Stachys chrysantha and Stachys Candida. Bio Pharmacol Bull, 2000; 23: 47 -53.
  • 44. Maleki N, Garjani A, Nazemiyah H, Nilfouroushan N, Eftekhar Sadat AT, Allameh Z et. al. Potent anti-inflammatory activities of hydroalcoholic extract from aerial parts of Stachys inflata on rats. J Ethnopharmacol, 2001; 75: 213–8.
  • 45. Takeda H, Ikeda Y. A model fort he origin of basaltic achondrites based on the Ysmsyo 7308 howardite. J Geophys Res Supp, 1995; 90: 649-3.
  • 46.Nash III TH. Lichen Biology, Cambridge: Cambridge University Press, 1996.
  • 47. Dobson FS. Lichens: An Illustrated Guide to the British and Irish Species. England: The Richmond Publishing, 2000.
  • 48.Dayan FE, Romagni JG. Lichens As a Potential Source of Pesticides. Pesticide Outlook, 2001; 12: 229-32.
  • 49. Ahmadjian V. The Lichen Symbiosis. New York: John Wiley and Sons, 1993.
  • 50.Shibata S, Ukita T, Tamura T, Miura Y. Relation between chemical constitutions and antibacterial effects of usnic acid and derivatives. Jap Med J, 1948; 1: 152–55.
  • 51. Jahns HM. Collins guide to ferns, mosses and lichens of Britain and Northern and Central Europe. Nordic J Bot, 1984; 4: 260.
  • 52.Toroğlu S, Çenet M. Tedavi amaçlı kullanılan bazı bitkilerin kullanım alanları ve antimikrobiyal aktivitelerinin belirlenmesi için kullanılan metodlar. KSU J Sci Eng, 2006; 9(2): 12- 20.
  • 53. Schindler H. Zur Geschichte der Anwendung von Flechten (Lichenes) in der Medizin. Carolinea, 1988; 4631- 46.
  • 54.Zeybek U, John V. Likenler, kimyasal bileşikleri ve tıbbi kullanımları. Pharmacia-JTPA, 1992; 32(1): 37- 48.
  • 55. Asahina Y. Lichenologische Notizen. J Jap Bot, 1967; 42: 289-94.
  • 56.Biswas K. Common medicinal plants of Darjeeling and the Sikkim-Himalayas, Sony Reprints Agency, New Delhi, 1956; 90.
  • 57. Huneck S, Yoshimura I. Identification of lichen substances. Berlin; Springer, 1996; 304- 49.
  • 58. Cook NC, Saman S, Flavonoids- Chemistry, metabolism, cardioprotective effects, and dietary sources. J Nutr Biochem, 1996; 7: 66- 76.
  • 59. Uysal H, Altun D, Aslan A. Drosophila melanogaster’de Lobaria pulmonaria (L.) Hoffm. Likeninin ömür uzunluğu üzerine etkisi. TÜBAV Bilim, 2009; 2(3): 271-76.
  • 60. Huneck S. The significanse of lichens and their metabolites. Naturwissenschaften, 1999; 86: 559-70.
  • 61. Miao V, Legal MFC, Brown D, Sinnemann S, Donaldson G, Davies J. Genetic approaches to harvesting lichen products. Trends in Biotechnol, 2001; 19: 349-355.
  • 62. Oran S. Liken Maddeleri (I). Liken maddelerinin liken yaşamındaki önemi. TLT Bülteni 2006; 3: 8-11.
  • 63.Brodo IM, Sharnoff SD, and Sharnoff S. Lichens of North America. London: Yale University Press, 2001.
  • 64.Culberson WL. Chemosystematics and ecology of lichens-forming fungi. Ann Rev Ecol Sys, 1970; 1: 153-70.
  • 65. Mitrović T, Stamenković S, Cvetković V, Tošić S, Stanković M, Radojević I et al. Antioxidant, antimicrobial and antiproliferative activities of five lichen species. Int J Mol Sci 2011; 12: 5428-48.
  • 66. Knop W. Chemisch-physiologische Untersuchung u ̈ ber die Flechten. Ann Chem Pharm, 1844; 49:103–24.
  • 67. Ahmadjian V, Hale ME. The Lichens. London: Academic Pres, 1973.
  • 68.Manojlovic NT, Solujic S, Sukdolak S. Antimicrobial activity of an extract and anthraquinones from Caloplaca schaereric. The British Lichen Society, 2002; 34:83–5.
  • 69. Müler K. Pharmaceutically relevant metabolites from lichens. Appl Microbiol Biotechnol, 2001; 56:9–16.
  • 70. Cansaran-Duman D. Türkiye’de bazı liken türlerindeki usnik asitin HPLC yöntemi ile değerlendirilmesi ve antimikrobiyal aktiviteleri. Turk Hij Den Biyol Derg, 2010; 66(4): 153-60.
  • 71. Cansaran-Duman D. Farklı liken örneklerindeki usnik asit miktarlarının yüksek basınçlı sıvı kromatografisi (HPLC) yöntemi ile belirlenmesi ve antimikrobiyal aktiviteleri. Turk Hij Den Biyol Derg, 2007; 64(3): 17-21.
  • 72. Kupchan SM, Kopperman HL. L–usnic acid: tumor inhibitor isolated from lichens. Experientia, 1975; 31: 625.
  • 73. Takai M, Uehara Y, Beisler JA. Usnic acid derivatives as potential antineoplastic agents. J Med Chem, 1979; 22: 1380–84.
  • 74.Backorova M, Backor M, Mikeš J, Jendzelovsky R, Fedorocko P. Variable responses of different human cancer cells to the lichen compounds parietin, atranorin, usnic acid and gyrophoric acid. Toxicol in Vitro, 2011; 25: 37-44.
  • 75. Zeytinoglu H, Incesu Z, Ayaz Tuylu B, Turk AO, Barutca B. Determination of genotoxic, antigenotoxic and cytotoxic potential of the extract from lichen cetraria aculeata (Schreb.) Fr. in vitro. Phytother Res, 2008; 22: 118-23.
  • 76.Haraldsdottir S, Gudlaugsdottir E, Ingolfsdottir K, Ogmundsdottir HM. Anti proliferative effects of lichen-derived lipoxygenase inhibitors on twelve human cancer cell lines of different tissue origin in vitro. Planta Med, 2004; 70: 1098-100.
  • 77. Einarsdóttir E, Groeneweg J, Björnsdóttir GG, Harðardottir G, Omarsdóttir S, Ingólfsdóttir K et al. Cellular mechanisms of the anticancer effects of the lichen compound usnic acid. Planta Med, 2010; 76: 969-74.