Liken metabolitlerinin antikanser aktivite etkisinin moleküler düzeyde mekanizmaları

Abstract

Tarih boyunca doğal ürünlerden elde edilen bileşenler; tıp, eczacılık ve biyoloji gibi pek çok alanda kullanılmıştır. Kanser alanında doğal moleküller model olarak kullanılarak yeni ve önemli bazı ticari ilaçlar elde edilmiştir. Sitotoksik ajanların geliştirilmesi için yapılan çalışmalar yeni antikanser ilaçlarının keşfi için de önemli bir adım olmuştur. Doğal bileşenlerin geniş yapısal çeşitliliği ve biyoaktivite potansiyeli moleküler modifikasyonlarla terapötik potansiyellerini geliştirmeye hizmet edebilir. Bu amaçla; özellikle son birkaç yılda liken kaynaklı bileşenlerin antikanser aktivitesiyle ilgili yapılan çalışmalar hızla artmaktadır. Likenler; fungus, alg veya siyanobakterilerin bir araya gelerek oluşturdukları simbiyotik birlikteliklerdir. Likenler, çoğu kendine özgü çok fazla sayıda sekonder metabolit sentezlerler. Liken sekonder metabolitleri antiviral, antitümör, antibakteriyel, antiherbivor ve antioksidan olmak üzere pek çok biyolojik aktiviteye sahiptirler. Son yıllarda liken sekonder metabolitlerinin tıbbi ve biyoteknolojik alanda dikkat çeken en önemli özelliklerinden birisi de kanser tedavisinde aday molekül olabileceklerine dair sonuçların ortaya çıkmasıdır. Kanserin moleküler temelleri ve özellikle apoptoz yolağı ile ilişkili süreçlerin aydınlatılması kanser tedavisinde alternatif ilaçların bulunmasında büyük bir yarar sunacağı düşünülmektedir. Bu derlemede; liken sekonder metabolitleri, kanser tedavisinde etkin kullanım potansiyelleri ve kanserleşme sürecinde özellikle apoptoz yolağı başta olmak üzere tüm moleküler mekanizmalar hakkında bilgi sunulmaktadır

Keywords

• liken sekonder metabolitleri, kanser, moleküler mekanizmalar

The Molecular Mechanisms of the effect of anticancer activity on lichen metabolites

Abstract

The components obtained from natural products have been used in many fields such as medicine, pharmacy and biology throughout the history. Some new and important commercial drugs have been obtained by using as a natural molecule model in the cancer field. Studies for the development of cytotoxic agents were also an important step for the discovery of new anticancer drugs. Large structural diversity of natural components and their bioactivity potential may serve to improve the therapeutic potential with molecular modification. For this purpose, especially the number of studies on the anticancer activity of lichen components has increased in last few years. Lichens are symbiotic organisms compose of fungus and algae or cyanobacteria. Lichens synthesize a great variety of secondary metabolites spesifically. Lichen secondary compounds have many possible biological activities such as antiviral, antitumor, antibacterial and antiherbivore and antioxidants. In recent years, one of the most important features of lichen secondary metabolites in medical and biotechnological field is the emmergance of results that maybe candidate molecules in the treatment of cancer. Elucidation of the molecular basis of cancer related processes and especially apoptosis pathway ilaçların bulunmasında büyük bir yarar sunacağı düşünülmektedir. Bu derlemede; liken sekonder metabolitleri, kanser tedavisinde etkin kullanım potansiyelleri ve kanserleşme sürecinde özellikle apoptoz yolağı başta olmak üzere tüm moleküler mekanizmalar hakkında bilgi sunulmaktadır

Keywords

• lichen secondary metabolites, cancer, molecular mechanisms

References

1. Hanahan D, Weinberg RA. The hallmarks of cancer. Cell, 2000; 100: 57-70. Sharnoff S. Field guide to California lichens. New York: Yale Uni Pres, 2014. Nash III TH. Lichen Biology. Cambridge: Cambridge Uni Press, 1996.
2. Huneck S, Yoshimura I. Identification of lichen substances. Berlin: Springer Verlag, 1996. Vartia KO. Antibiotics in lichens, In: The Lichens (Ahmadjian V and Hale ME. Academic Press., New York, 1973; 547-61. Ingolfsdottir K. Usnic acid. Phytochem, 2002; 61: 729-36. Kristmundsdottir T, Jonsdottir E, Ogmundsdottir HM, Ingolfsdottir K. Solubilization of poorly soluble lichen metabolites for biological testing on celllines. Eur J Pharm Sci, 2005; 24, 539-43.
3. Honda NK, Pavan FR, Coelho RG, Leite SRD, Micheletti AC, Lopes TIB. Antimycobacterial activity of lichen substances. Phytomed, 2010; 17, 328-32. Bugni TS, Andjelic CD, Pole AR, Rai P, Ireland CM, Barrows LR. Biologically active components of a Papua New Guinea analgesic and anti inflammatory lichen preparation. Fitoterapia, 2009; 80, 270-3.
4. Melo MGD, Araujo AAS, Rocha CPL, Almeida EMSA, Siqueira RD, Bonjardim LR. Purificationi, physicochemical properties, thermal analysis and antinociceptive effect of atranorin extracted from Cladina kalbii. Biol Pharm Bull, 2008; 31: 1977-80.
5. Özenoğlu S, Aydoğdu G, Dinçsoy AB, Taghidizaj AA, Derici K, Yılmaz E, et al. Liken sekonder bileşiklerinin farklı insan kanser hücre tipleri üzerine antikanserojenik etkisi. Turk Hij ve Den Biyol Derg, 2013; 70-4: 215-26.
6. Stanojković T. Investigations of lichen secondary metabolites with potential anticancer activity. Lich Sec Met, 2015; 127-46.
7. Bačkorová M, Jendželovský R, Kello M. Lichen secondary metabolites are responsible for induction of apoptosis in HT-29 and A2780 human cancer cell lines. Toxicol in Vitro, 2012; 26: 462-8.
8. Brisdelli F, Perilli M, Sellitri D. Cytotoxic activity and antioxidant capacity of purified lichen metabolites: an in vitro study. Phytother Res, 2013; 27: 431-7.

9. Russo A, Caggia S, Piovano M. Effect of vicanicin and on human prostate cancer cells: role of Hsp70 protein. Chem Biol Interact, 2012; 195: 1-10.
10. Einarsdóttir E, Groeneweg J, Björnsdóttir GG. Cellular mechanisms of the anticancer effects of the lichen compound usnic acid. Planta Med, 2010; 76: 969-74.
11. O’Neill MA, Mayer M, Murray KE. Does usnic acid affect microtubules in human cancer cells? Braz J Biol, 2010; 70: 659-64.
12. Burlando B, Ranzato E, Volante A, Appendino G, Pollastro F, Verotta L. Antiproliferative effects on tumour cells and promotion of keratinocyte wound healing by different lichen compounds. Planta Med, 2009; 75: 607-13.
13. Bazin MA, Le-Lamer AC, Delcros JG. Synthesis and cytotoxic activities of usnic acid derivatives. Bioorg Med Chem, 2008; 16: 6860-6.
14. Koparal AT, Tüylü BA, Türk H. In vitro cytotoxic activities of (+) usnic acid and (-) usnic acid on V79, A549, and human lymphocyte cells and their non-genotoxicity on human lymphocytes. Nat Prod Res, 2006; 20 (14): 1300-7.
15. Mayer M, O’Neill MA, Murray KE. Usnic acid: a non- genotoxic compound with anti-cancer properties. Anticancer Drugs, 2005; 16: 805-9.
16. Bezivin C, Tomasi S, Rouaud I, Delcros JG, Boustie J. Cytotoxic activity of compounds from the lichen: Cladonia convoluta. Planta Med, 2004; 70: 874-7.
17. 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. Singh N, Nambiar D, Kale RK, Singh RP. Usnic acid inhibits growth and induces cell cycle arrest and apoptosis in human lung carcinoma A549 cells. Nutr Cancer, 2013; 65: 36-43.
18. Einarsdóttir E, Groeneweg J, Björnsdóttir GG. Cellular mechanisms of the anticancer effects of the lichen compound usnic acid. Planta Med, 2010; 76: 969-74.
19. Backorova M, Backor M, Mikes 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.
20. Bačkorová M, Jendželovský R, Kello M. Lichen secondary metabolites are responsible for induction of apoptosis in HT-29 and A2780 human cancer cell lines. Toxicol In Vitro, 2012; 26: 462-8.
21. Jin JQ, Li CQ, He LC. Down-regulatory effect of usnic acid on nuclear factor-kappa B-dependent tumor necrosis factor-alpha and inducible nitric oxide synthase expression in lipopolysaccharide- stimulated macrophages RAW. Phytother Res, 2008; 22: 1605-9.
22. Song Y, Dai F, Zhai D, Dong Y, Zhang J, Lu B, et al. Usnic acid inhibits breast tumor angiogenesis and growth by suppressing VEGFR2- mediated AKT and ERK1/2 signaling pathways. Angiogenesis, 2012; 15: 421-32.
23. Koparal AT, Ulus G, Zeytinoglu M, Tay T, Turk AO. Angiogenesis inhibition by a lichen compound olivetoric acid. Phytother Res, 2010; 24: 754–8.
24. Seo C, Yim JH, Lee HK, Oh H. PTP1B inhibitory secondary metabolites from the Antarctic lichen Lecidella carpathica. Mycology, 2011; 2: 18–23.
25. Letai AG. Diagnosing and exploiting cancer’s addiction to blocks in apoptosis. Nat Rev Canc, 2008; 8: 121-32.
26. Riedl SJ, Salvesen GS. The apoptosome: signalling platform of cell death. Nat Rev Mol Cell Biol, 2007; 8: 405-13.
27. Basile A, Rigano D, Loppi S, Di Santi A, Nebbioso A, Sorbo S, et al. Antiproliferative, antibacterial and antifungal activity of the lichen Xanthoria parietina and its secondary metabolite parietin. Int J Mol Sci, 2015; 16 (4): 7861-75.
28. Singh N, Nambiar D, Kale RK, Singh RP. Usnic acid inhibits growth and induces cell cycle arrest and apoptosis in human lung carcinoma A549 cells. Nutr Cancer, 2013; 65: 36-43.
29. Nguyen TT, Yoon S, Yang Y, Lee HB, Oh S, Jeong MH, et al. Lichen secondary metabolites in Flavocetraria cucullata exhibit anti-cancer effects on human cancer cells through the induction of apoptosis and suppression of tumorigenic potentials. PLoS One, 2014; 31: 9 (10):e111575.