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Usnic acid uses mitochondrial apopitotic pathway in it’s antitumoral role

Yıl 2017, Cilt: 39 Sayı: 3, 539 - 545, 19.09.2017
https://doi.org/10.7197/223.v39i31705.347452

Öz

Objective: Usnic
acid is a secondary metabolite in lichens whose role has not been completely
elucidated. Lichen extracts containing usnic acid have been utilized in
medicine, perfumery, cosmetics, and ecology. Usnic asit inhibits cell growth,
induces the cell cycle arrest and apoptosis in human lung carcinoma.

Methods:Herein we
analyzed the antitumoral effect of usnic acid on the same cell line. We
analyzed the gene expression results on APOPT1,
CYCS, APAF1, CASP3/9,
TNF, BCL2, BCL2L1 and AIFM1
genes which have possible role on cell apopitosis.

Results: Usnic
acid has stimulatory effect on APOPT1,
CYCS, APAF1, CASP3, CASP9
gene expressions in our experiments.







Conclusion: Usnic acid has antitumoral effect on cancer cells, affecting on
mithocondrial apopitotic genes. 

Kaynakça

  • 1. Cocchietto M, Skert N, Nimis PL, Sava G. A review on usnic acid, an interesting natural compound. Naturwissenschaften 2002; 89: 137-46.
  • 2. Ingólfsdóttir K. Usnic acid. Phytochemistry 2002; 61:729-36.
  • 3. Periera EC, Nascimento SC, Lima RC, Silva NH, Oliveira AF, Bandeira E, Boitard M, Beriel H, Vicente C, Legaz ME. Analysis of Usnea fasciata crude extracts with antineoplastic activity. Tokai J Exp Clin Med 1994; 19: 47-52.
  • 4. O'Neill MA1, Mayer M, Murray KE, Rolim-Santos HM, Santos-Magalhães NS, Thompson AM, Appleyard VC. Does usnic acid affect microtubules in human cancer cells? Braz J Biol. 2010; 70: 659-64.
  • 5. Cardarelli M, Serino G, Campanella L, Ercole P, De Cicco Nardone F, Alesiani O, Rossiello F. Antimitotic effects of usnic acid on different biological systems. Cellular and Molecular Life Sciences CMLS 1997; 53: 667-72.
  • 6. 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: Suppl 1: 36-43.
  • 7. Sun X, Yasuda O, Takemura Y, Kawamoto H, Higuchi M, Baba Y, Katsuya T, Fukuo K, Ogihara T, Rakugi H. Akt activation prevents Apop-1-induced death of cells. Biochem Biophys Res Commun. 2008; 377: 1097-101.
  • 8. Tafani M, Karpinich NO, Hurster KA, Pastorino JG, Schneider T, Russo MA, Farber JL. Cytochrome c release upon Fas receptor activation depends on translocation of full-length bid and the induction of the mitochondrial permeability transition. J Biol Chem 2002; 277: 10073-82.
  • 9. Fujimoto A, Takeuchi H, Taback B, Hsueh EC, Elashoff D, Morton DL, Hoon DS. Allelic imbalance of 12q22-23 associated with APAF-1 locus correlates with poor disease outcome in cutaneous melanoma. Cancer Res. 2004; 64: 2245-50.
  • 10. González D, Espino J, Bejarano I, López JJ, Rodríguez AB, Pariente JA. Caspase-3 and -9 are activated in human myeloid HL-60 cells by calcium signal. Mol Cell Biochem 2010; 333: 151-7.
  • 11. Read RC, Teare DM, Pridmore AC, Naylor SC, Timms JM, Kaczmarski EB, Borrow R, Wilson AG. The tumor necrosis factor polymorphism TNF (-308) is associated with susceptibility to meningococcal sepsis, but not with lethality. Crit Care Med 2009; 37: 1237-43.
  • 12. Chiorazzi M, Rui L, Yang Y, Ceribelli M, Tishbi N, Maurer CW, Ranuncolo SM, Zhao H, Xu W, Chan WC, Jaffe ES, Gascoyne RD, Campo E, Rosenwald A, Ott G, Delabie J, Rimsza LM, Shaham S, Staudt LM. Related F-box proteins control cell death in Caenorhabditis elegans and human lymphoma. Proc Natl Acad Sci U S A 2013; 110: 3943-8.
  • 13. Wang J, Beauchemin M, Bertrand R. Bcl-xL phosphorylation at Ser49 by polo kinase 3 during cell cycle progression and checkpoints. Cell Signal 2011; 23: 2030-8.
  • 14. Rinaldi C, Grunseich C, Sevrioukova IF, Schindler A, Horkayne-Szakaly I, Lamperti C, Landouré G, Kennerson ML, Burnett BG, Bönnemann C, Biesecker LG, Ghezzi D, Zeviani M, Fischbeck KH. Cowchock syndrome is associated with a mutation in apoptosis-inducing factor. Am J Hum Genet 2012; 91: 1095-102.
  • 15. Gülşen MR, Uzunay NS, Fermanlı O, Çoban ZD, Öztürk D, Hamidi M, Avcu F, Güran Ş. Anti-angiogenic role of Ankaferd on chick chorioallontoic membrane model. Gülhane Medical Journal 2015; 57: 274-9.
  • 16. Kilicoglu B, Kismet K, Koru O, Tanyuksel M, Oruc MT, Sorkun K, Akkus MA. The scolicidal effects of honey. Adv Ther 2006; 23: 1077-83.
  • 17. Tong Z, Qu S, Zhang J, Wang F, Tao J, Gao Z, Zhang Z. A modified protocol for RNA extraction from different peach tissues suitable for gene isolation and Real-Time PCR Analysis. Molecular Biotechnology 2012; 50: 229-36.
  • 18. Bačkorová M, Bačkor M, Mikeš J, Jendželovský R, Fedoročko 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.
  • 19. O'Neill MA, Mayer M, Murray KE, Rolim-Santos HM, Santos-Magalhães NS, Thompson AM, Appleyard VC. Does usnic acid affect microtubules in human cancer cells? Braz J Biol 2010; 70: 659-64.
  • 20. Brisdelli F, Perilli M, Sellitri D, Piovano M, Garbarino JA, Nicoletti M, Bozzi A, Amicosante G, Celenza G. Cytotoxic activity and antioxidant capacity of purified lichen metabolites: an in vitro study. Phytother Res 2013; 27: 431-7.
  • 21. Hassan M, Watari H, Almaaty AA, Ohba Y, Sakuragi N. Apoptosis and Molecular Targeting Therapy in Cancer. Biomed Res Int 2014; 2014: 150845.
  • 22. Locksley RM, Killeen N, Lenardo MJ. The TNF and TNF receptor superfamilies: integrating mammalian biology. Cell 2001; 104: 487-501.
  • 23. Green DR, Kroemer G. The pathophysiology of mitochondrial cell death. Science 2004; 305(5684): 626-9.
  • 24. Motyka B, Korbutt G, Pinkoski MJ, et al. Mannose 6-phosphate/insulin-like growth factor II receptor is a death receptor for granzyme B during cytotoxic T cell-induced apoptosis. Cell 2000; 103: 491-500.
  • 25. Sun X, Yasuda O, Takemura Y, Kawamoto H, Higuchi M, Baba Y, Katsuya T, Fukuo K, Ogihara T, Rakugi H. Akt activation prevents Apop-1-induced death of cells. Biochem Biophys Res Commun 2008; 377: 1097-101.
  • 26. Morison IM, Cramer Bordé EM, Cheesman EJ, Cheong PL, Holyoake AJ, Fichelson S, Weeks RJ, Lo A, Davies SM, Wilbanks SM, Fagerlund RD, Ludgate MW, da Silva Tatley FM, Coker MS, Bockett NA, Hughes G, Pippig DA, Smith MP, Capron C, Ledgerwood EC. A mutation of human cytochrome c enhances the intrinsic apoptotic pathway but causes only thrombocytopenia. Nat Genet 2008; 40: 387-9.
  • 27. Vakifahmetoglu-Norberg H, Ouchida AT2, Norberg E3. The role of mitochondria in metabolism and cell death. Biochem Biophys Res Commun 2017 15; 482: 426-31.
  • 28. Apostolaki M, Armaka M, Victoratos P, Kollias G. Cellular mechanisms of TNF function in models of inflammation and autoimmunity. Curr Dir Autoimmun 2010; 11:1-26.
  • 29. Lee HC, Wei YH. Mitochondrial role in life and death of the cell. J Biomed Sci 2000; 7: 2-15.

Usnik asitin tümör önleyici rolü mitokondrial apopitotik yolak üzerindedir

Yıl 2017, Cilt: 39 Sayı: 3, 539 - 545, 19.09.2017
https://doi.org/10.7197/223.v39i31705.347452

Öz

Amaç: Usnik asit likenlerde bulunan halen rolü tam olarak ortaya
konamamış bir sekonder metabolittir. Usnik asit içeren liken ekstraktları
tıpta, parfüm yapımında, kozmetikte ve ekolojide kullanılmaktadır. Usnik asit
insan akciğer kanserinde hücre büyümesini durdurmakta, hücre döngüsünün
durdurulması ve apopitozu aktive etmektedir. Çalışmamızda aynı hücre hattında
usnik asitin antitümöral etkisi bakılmıştır.

Yöntem: Hücre apopitozunda rolü olan APOPT1, CYCS, APAF1, CASP3/9, TNF,
BCL2
ve
BCL2L1
genlerinin
ekspresyon analizine bakıldı.

Bulgular: Usnik asitin APOPT1, CYCS, APAF1, CASP3, CASP9 genleri üzerinde uyarıcı etkisi olduğu
saptandı.







Sonuç: Veriler usnik asitin kanser hücreleri üzerinde
mitokondrial apopitotik genler aracılığı ile antitümöral etki yaptığını ortaya
koymaktadır.

Kaynakça

  • 1. Cocchietto M, Skert N, Nimis PL, Sava G. A review on usnic acid, an interesting natural compound. Naturwissenschaften 2002; 89: 137-46.
  • 2. Ingólfsdóttir K. Usnic acid. Phytochemistry 2002; 61:729-36.
  • 3. Periera EC, Nascimento SC, Lima RC, Silva NH, Oliveira AF, Bandeira E, Boitard M, Beriel H, Vicente C, Legaz ME. Analysis of Usnea fasciata crude extracts with antineoplastic activity. Tokai J Exp Clin Med 1994; 19: 47-52.
  • 4. O'Neill MA1, Mayer M, Murray KE, Rolim-Santos HM, Santos-Magalhães NS, Thompson AM, Appleyard VC. Does usnic acid affect microtubules in human cancer cells? Braz J Biol. 2010; 70: 659-64.
  • 5. Cardarelli M, Serino G, Campanella L, Ercole P, De Cicco Nardone F, Alesiani O, Rossiello F. Antimitotic effects of usnic acid on different biological systems. Cellular and Molecular Life Sciences CMLS 1997; 53: 667-72.
  • 6. 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: Suppl 1: 36-43.
  • 7. Sun X, Yasuda O, Takemura Y, Kawamoto H, Higuchi M, Baba Y, Katsuya T, Fukuo K, Ogihara T, Rakugi H. Akt activation prevents Apop-1-induced death of cells. Biochem Biophys Res Commun. 2008; 377: 1097-101.
  • 8. Tafani M, Karpinich NO, Hurster KA, Pastorino JG, Schneider T, Russo MA, Farber JL. Cytochrome c release upon Fas receptor activation depends on translocation of full-length bid and the induction of the mitochondrial permeability transition. J Biol Chem 2002; 277: 10073-82.
  • 9. Fujimoto A, Takeuchi H, Taback B, Hsueh EC, Elashoff D, Morton DL, Hoon DS. Allelic imbalance of 12q22-23 associated with APAF-1 locus correlates with poor disease outcome in cutaneous melanoma. Cancer Res. 2004; 64: 2245-50.
  • 10. González D, Espino J, Bejarano I, López JJ, Rodríguez AB, Pariente JA. Caspase-3 and -9 are activated in human myeloid HL-60 cells by calcium signal. Mol Cell Biochem 2010; 333: 151-7.
  • 11. Read RC, Teare DM, Pridmore AC, Naylor SC, Timms JM, Kaczmarski EB, Borrow R, Wilson AG. The tumor necrosis factor polymorphism TNF (-308) is associated with susceptibility to meningococcal sepsis, but not with lethality. Crit Care Med 2009; 37: 1237-43.
  • 12. Chiorazzi M, Rui L, Yang Y, Ceribelli M, Tishbi N, Maurer CW, Ranuncolo SM, Zhao H, Xu W, Chan WC, Jaffe ES, Gascoyne RD, Campo E, Rosenwald A, Ott G, Delabie J, Rimsza LM, Shaham S, Staudt LM. Related F-box proteins control cell death in Caenorhabditis elegans and human lymphoma. Proc Natl Acad Sci U S A 2013; 110: 3943-8.
  • 13. Wang J, Beauchemin M, Bertrand R. Bcl-xL phosphorylation at Ser49 by polo kinase 3 during cell cycle progression and checkpoints. Cell Signal 2011; 23: 2030-8.
  • 14. Rinaldi C, Grunseich C, Sevrioukova IF, Schindler A, Horkayne-Szakaly I, Lamperti C, Landouré G, Kennerson ML, Burnett BG, Bönnemann C, Biesecker LG, Ghezzi D, Zeviani M, Fischbeck KH. Cowchock syndrome is associated with a mutation in apoptosis-inducing factor. Am J Hum Genet 2012; 91: 1095-102.
  • 15. Gülşen MR, Uzunay NS, Fermanlı O, Çoban ZD, Öztürk D, Hamidi M, Avcu F, Güran Ş. Anti-angiogenic role of Ankaferd on chick chorioallontoic membrane model. Gülhane Medical Journal 2015; 57: 274-9.
  • 16. Kilicoglu B, Kismet K, Koru O, Tanyuksel M, Oruc MT, Sorkun K, Akkus MA. The scolicidal effects of honey. Adv Ther 2006; 23: 1077-83.
  • 17. Tong Z, Qu S, Zhang J, Wang F, Tao J, Gao Z, Zhang Z. A modified protocol for RNA extraction from different peach tissues suitable for gene isolation and Real-Time PCR Analysis. Molecular Biotechnology 2012; 50: 229-36.
  • 18. Bačkorová M, Bačkor M, Mikeš J, Jendželovský R, Fedoročko 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.
  • 19. O'Neill MA, Mayer M, Murray KE, Rolim-Santos HM, Santos-Magalhães NS, Thompson AM, Appleyard VC. Does usnic acid affect microtubules in human cancer cells? Braz J Biol 2010; 70: 659-64.
  • 20. Brisdelli F, Perilli M, Sellitri D, Piovano M, Garbarino JA, Nicoletti M, Bozzi A, Amicosante G, Celenza G. Cytotoxic activity and antioxidant capacity of purified lichen metabolites: an in vitro study. Phytother Res 2013; 27: 431-7.
  • 21. Hassan M, Watari H, Almaaty AA, Ohba Y, Sakuragi N. Apoptosis and Molecular Targeting Therapy in Cancer. Biomed Res Int 2014; 2014: 150845.
  • 22. Locksley RM, Killeen N, Lenardo MJ. The TNF and TNF receptor superfamilies: integrating mammalian biology. Cell 2001; 104: 487-501.
  • 23. Green DR, Kroemer G. The pathophysiology of mitochondrial cell death. Science 2004; 305(5684): 626-9.
  • 24. Motyka B, Korbutt G, Pinkoski MJ, et al. Mannose 6-phosphate/insulin-like growth factor II receptor is a death receptor for granzyme B during cytotoxic T cell-induced apoptosis. Cell 2000; 103: 491-500.
  • 25. Sun X, Yasuda O, Takemura Y, Kawamoto H, Higuchi M, Baba Y, Katsuya T, Fukuo K, Ogihara T, Rakugi H. Akt activation prevents Apop-1-induced death of cells. Biochem Biophys Res Commun 2008; 377: 1097-101.
  • 26. Morison IM, Cramer Bordé EM, Cheesman EJ, Cheong PL, Holyoake AJ, Fichelson S, Weeks RJ, Lo A, Davies SM, Wilbanks SM, Fagerlund RD, Ludgate MW, da Silva Tatley FM, Coker MS, Bockett NA, Hughes G, Pippig DA, Smith MP, Capron C, Ledgerwood EC. A mutation of human cytochrome c enhances the intrinsic apoptotic pathway but causes only thrombocytopenia. Nat Genet 2008; 40: 387-9.
  • 27. Vakifahmetoglu-Norberg H, Ouchida AT2, Norberg E3. The role of mitochondria in metabolism and cell death. Biochem Biophys Res Commun 2017 15; 482: 426-31.
  • 28. Apostolaki M, Armaka M, Victoratos P, Kollias G. Cellular mechanisms of TNF function in models of inflammation and autoimmunity. Curr Dir Autoimmun 2010; 11:1-26.
  • 29. Lee HC, Wei YH. Mitochondrial role in life and death of the cell. J Biomed Sci 2000; 7: 2-15.
Toplam 29 adet kaynakça vardır.

Ayrıntılar

Konular Sağlık Kurumları Yönetimi
Bölüm Basic Science Research Makaleler
Yazarlar

Zehra Dilşad Çoban

Tuna Karaer

Büşra Atmaca

Halide Kaya Demir

Şefik Güran

Yayımlanma Tarihi 19 Eylül 2017
Kabul Tarihi 1 Haziran 2017
Yayımlandığı Sayı Yıl 2017Cilt: 39 Sayı: 3

Kaynak Göster

AMA Çoban ZD, Karaer T, Atmaca B, Kaya Demir H, Güran Ş. Usnic acid uses mitochondrial apopitotic pathway in it’s antitumoral role. CMJ. Eylül 2017;39(3):539-545. doi:10.7197/223.v39i31705.347452