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İnsan Meme Kanseri Hücre Serileri MCF-7 Üzerine Apelin-13’ün Etkilerinin Araştırılması: In Vitro Bir Çalışma

Year 2013, Volume: 2 Issue: 1, 23 - 28, 01.04.2013

Abstract

Apelin, G protein kenetli orfan apelin reseptörünün APJ endojen ligantıdır. Apelinin hipotalamusta özellikle arkuat, supraoptik veparaventriküler nükleus gibi hipotalamik alanlarda dağılım göstermesi testis, prostat ve meme dokusunda APJ’nin bulunması, üremesistemi üzerinde apelinin önemli fizyolojik etkilerinin olabileceğini akla getirmektedir. Apelinin yapısındaki 13 amino asit dizilimi tümformlarında değişmez olduğundan, temel apelin yapısı apelin-13 olarak kabul edilmektedir. Bu çalışmada ilk olarak, östrojen duyarlı insanmeme kanseri hücre hattına MCF–7 , apelin–13’ün 0.1, 1 ve 10 nM'lık konsantrasyonları, östrojen hormonunun 1, 10, 100 nM’likkonsantrasyonları uygulandı. Daha sonra apelinin, 1 ve 10 nM olan dozları ile östrojen hormonunun 1, 10, 100 nM’lik dozları eş zamanlıolarak kültüre uygulandı ve 24 saat inkübe edildi. Bu maddelerin MCF-7 hücre canlılığı üzerine etkileri, 3- 4,5-dimethylthiazol-2-yl -2,5diphenyltetrazolium bromide MTT assay ile belirlendi. Sonuçlar, % hücre canlılık değeri olarak belirlendi. MCF–7 hücre hattınauygulanan apelin-13’ün hücre canlılığını azalttığı p0.05 . Apelin-13’ün,MCF-7 hücre serilerinde canlılığı azaltması östrojen indüklemeli gruplarda dahil poliferatif etkinin östrojen reseptör kaynaklı olduğunuve apelin-13’ün anti-kanserojenik bir ajan olarak kullanılabileceğini akla getirmektedir

References

  • 1. WHO, Dünya Kanser Raporu 2008, ed. P. Boyle, B. Levin2008, Lyon.
  • 2. Meites J. Relation of prolactin and estrogen to mammary tumorigenesis in the rat. J Natl Cancer Inst 1972; 48(4): 1217-24.
  • 3. Cuzick J, Wang DY, Bulbrook RD. The prevention of breast cancer. Lancet 1986; 1(8472): 83-6.
  • 4. Santen RJ, Boyd NF, Chlebowski RT, Cummings S, Cuzick J, Dowsett M, Easton D, Forbes JF, Key T, Hankinson SE, Howell A, Ingle J. Critical assessment of new risk factors for breast cancer: considerations for development of an improved risk prediction model. Endocr Relat Cancer 2007; 14(2): 169-87.
  • 5. Dieudonne MN, Bussiere M, Dos Santos E, Leneveu MC, Giudicelli Y, Pecquery R. Adiponectin mediates antiproliferative and apoptotic responses in human MCF7 breast cancer cells. Biochem Biophys Res Commun 2006; 345(1): 271-9.
  • 6. Tatemoto K, Hosoya M, Habata Y, Fujii R, Kakegawa T, Zou MX, Kawamata Y, Fukusumi S, Hinuma S, Kitada C, Kurokawa T, Onda H, Fujino M. Isolation and characterization of a novel endogenous peptide ligand for the human APJ receptor. Biochemical and Biophysical Research Communications 1998; 251(2): 471-476.
  • 7. Hinuma S, Onda H, Fujino M. The quest for novel bioactive peptides utilizing orphan seventransmembrane-domain receptors. J Mol Med (Berl) 1999; 77(6): 495-504.
  • 8. Todisco A, Campbell V, Dickinson CJ, DelValle J, Yamada T. Molecular basis for somatostatin action: inhibition of c-fos expression and AP-1 binding. Am J Physiol 1994; 267(2 Pt 1): G245-53.
  • 9. Hosoya M, Kawamata Y, Fukusumi S, Fujii R, Habata Y, Hinuma S, Kitada C, Honda S, Kurokawa T, Onda H, Nishimura O, Fujino M. Molecular and functional characteristics of APJ. Tissue distribution of mRNA and interaction with the endogenous ligand apelin. J Biol Chem 2000; 275(28): 21061-7.
  • 10. Kawamata Y, Habata Y, Fukusumi S, Hosoya M, Fujii R, Hinuma S, Nishizawa N, Kitada C, Onda H, Nishimura O, Fujino M. Molecular properties of apelin: tissue distribution and receptor binding. Biochim Biophys Acta 2001; 1538(2-3): 162-71.
  • 11. Habata Y, Fujii R, Hosoya M, Fukusumi S, Kawamata Y, Hinuma S, Kitada C, Nishizawa N, Murosaki S, Kurokawa T, Onda H, Tatemoto K, Fujino M. Apelin, the natural ligand of the orphan receptor APJ, is abundantly secreted in the colostrum. Biochimica et Biophysica Acta (BBA) - Molecular Cell Research 1999; 1452(1): 25-35.
  • 12. Wang G, Anini Y, Wei W, Qi X, O’Carroll A-M, Mochizuki T, Wang H-Q, Hellmich MR, Englander EW, Greeley GH. Apelin, a New Enteric Peptide: Localization in the Gastrointestinal Tract, Ontogeny, and Stimulation of Gastric Cell Proliferation and of Cholecystokinin Secretion. Endocrinology 2004; 145(3): 1342-1348.
  • 13. Wang G, Qi X, Wei W, Englander EW, Greeley GH, Jr. Characterization of the 5'-regulatory regions of the rat and human apelin genes and regulation of breast apelin by USF. FASEB J 2006; 20(14): 2639- 41.
  • 14. Wang Z, Greeley GH, Jr., Qiu S. Immunohistochemical localization of apelin in human normal breast and breast carcinoma. J Mol Histol 2008; 39(1): 121-4.
  • 15. Denizot F, Lang R. Rapid colorimetric assay for cell growth and survival: Modifications to the tetrazolium dye procedure giving improved sensitivity and reliability. Journal of Immunological Methods 1986; 89(2): 271-277.
  • 16. Horakova K, Sovcikova A, Seemannova Z, Syrova D, Busanyova K, Drobna Z, Ferencik M. Detection of drug-induced, superoxide-mediated cell damage and its prevention by antioxidants. Free Radic Biol Med 2001; 30(6): 650-64.
  • 17. Mosmann T. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods 1983; 65(1- 2): 55-63.
  • 18. Ray A. Adipokine leptin in obesity-related pathology of breast cancer. J Biosci 2012; 37(2): 289-94.
  • 19. Yaşartürk Ü, Altıntaş A. Meme Tümörlü Köpeklerde Serum 17β-estradiol Kolesterol ve Trigliserid Düzeylerinin Klinik Önemi. F.Ü.Sağ.Bil.Vet.Derg. 2010; 24(3): 157-161.
  • 20. Henderson BE, Ross R, Bernstein L. Estrogens as a Cause of Human Cancer: The Richard and Hinda Rosenthal Foundation Award Lecture. Cancer Research 1988; 48(2): 246-253
  • 21. Carlstrom K. Influence of intratumoral estradiol biosynthesis on estrogen receptors. Recent Results Cancer Res 1984; 91: 145-9.
  • 22. Osborne CK. Tamoxifen in the treatment of breast cancer. N Engl J Med 1998; 339(22): 1609-18.
  • 23. Gimble JM. Adipose tissue-derived therapeutics. Expert Opin Biol Ther 2003; 3(5): 705-13.
  • 24. Wozniak SE, Gee LL, Wachtel MS, Frezza EE. Adipose tissue: the new endocrine organ? A review article. Dig Dis Sci 2009; 54(9): 1847-56.
  • 25. Liu Y, Song CY, Wu SS, Liang QH, Yuan LQ, Liao EY. Novel adipokines and bone metabolism. Int J Endocrinol 2013; 2013: 895045.
  • 26. Popkin BM. Understanding global nutrition dynamics as a step towards controlling cancer incidence. Nat Rev Cancer 2007; 7(1): 61-7.
  • 27. Zhang Y, Proenca R, Maffei M, Barone M, Leopold L, Friedman JM. Positional cloning of the mouse obese gene and its human homologue. Nature 1994; 372(6505): 425-32.
  • 28. Garofalo C, Surmacz E. Leptin and cancer. J Cell Physiol 2006; 207(1): 12-22.
  • 29. Mantzoros C, Petridou E, Dessypris N, Chavelas C, Dalamaga M, Alexe DM, Papadiamantis Y, Markopoulos C, Spanos E, Chrousos G, Trichopoulos D. Adiponectin and breast cancer risk. J Clin Endocrinol Metab 2004; 89(3): 1102-7.
  • 30. Miyoshi Y, Funahashi T, Kihara S, Taguchi T, Tamaki Y, Matsuzawa Y, Noguchi S. Association of serum adiponectin levels with breast cancer risk. Clin Cancer Res 2003; 9(15): 5699-704.
  • 31. Matsubara M, Maruoka S, Katayose S. Inverse relationship between plasma adiponectin and leptin concentrations in normal-weight and obese women. European Journal of Endocrinology 2002; 147(2): 173-180.
  • 32. Kim JG, Kim EO, Jeong BR, Min YJ, Park JW, Kim ES, Namgoong IS, Kim YI, Lee BJ. Visfatin stimulates proliferation of MCF-7 human breast cancer cells. Mol Cells 2010; 30(4): 341-5.
  • 33. Somasundar P, Yu AK, Vona-Davis L, McFadden DW. Differential effects of leptin on cancer in vitro. J Surg Res 2003; 113(1): 50-5.
  • 34. Catalano S, Mauro L, Marsico S, Giordano C, Rizza P, Rago V, Montanaro D, Maggiolini M, Panno ML, Ando S. Leptin induces, via ERK1/ERK2 signal, functional activation of estrogen receptor alpha in MCF-7 cells. J Biol Chem 2004; 279(19): 19908-15.
  • 35. Grossmann ME, Nkhata KJ, Mizuno NK, Ray A, Cleary MP. Effects of adiponectin on breast cancer cell growth and signaling. Br J Cancer 2008; 98(2): 370-9.
  • 36. Berta J, Kenessey I, Dobos J, Tovari J, Klepetko W, Jan Ankersmit H, Hegedus B, Renyi-Vamos F, Varga J, Lorincz Z, Paku S, Ostoros G, Rozsas A, Timar J, Dome B. Apelin expression in human non- small cell lung cancer: role in angiogenesis and prognosis. J Thorac Oncol 2010; 5(8): 1120-9.
  • 37. Heo K, Kim YH, Sung HJ, Li HY, Yoo CW, Kim JY, Park JY, Lee UL, Nam BH, Kim EO, Kim SY, Lee SH, Park JB, Choi SW. Hypoxia-induced upregulation of apelin is associated with a poor prognosis in oral squamous cell carcinoma patients. Oral Oncology 2012; 48(6): 500-506.

The Investigation of The Effects of Apelin on Human Breast Cancer Cell Lines MCF-7 : An In Vitro Study

Year 2013, Volume: 2 Issue: 1, 23 - 28, 01.04.2013

Abstract

Apelin is the endogenous ligand for the G-protein-coupled APJ receptor. Apelin has been found in hypothalamic fields such as theparaventricular nucleus and supraoptic nucleus of the hypothalamus and it is seen in testicle, prostate and mammary tissues. Thereforeapelin may be influential on productive system. Apelin show the distribution the hypothalamus, especially the arcuate, supraoptic nucleusand such as paraventricular hypothalamic areas. Presence of APJ in the testicles, the prostate tissue, breast tissue, suggests that apelin maybe important physiological effects on the reproductive system. As the sequence of 13 amino acids in apelin can not be changed, the basicapelin structure is accepted as apelin-13. In the study, firstly, 0.1, 1 and 10 μM concentrations of apelin–13 and 1, 10, 100 μMconcentrations of estrogen were applied into the line of estrogen sensitive breast cancer cell MCF–7 . Apelin 0.1, 1 and 10 μM andestrogen hormone 1, 10, 100 μM were simultaneously cultured and incubated for 24 hours and their effectiveness were detected by meansof 3- 4,5-dimethylthiazol–2-yl -2,5-diphenyltetrazolium bromide MTT . It has been detected that apelin–13 applied into MCF–7 linedecreases the cell liveliness, and estrogen increases cell liveliness p

References

  • 1. WHO, Dünya Kanser Raporu 2008, ed. P. Boyle, B. Levin2008, Lyon.
  • 2. Meites J. Relation of prolactin and estrogen to mammary tumorigenesis in the rat. J Natl Cancer Inst 1972; 48(4): 1217-24.
  • 3. Cuzick J, Wang DY, Bulbrook RD. The prevention of breast cancer. Lancet 1986; 1(8472): 83-6.
  • 4. Santen RJ, Boyd NF, Chlebowski RT, Cummings S, Cuzick J, Dowsett M, Easton D, Forbes JF, Key T, Hankinson SE, Howell A, Ingle J. Critical assessment of new risk factors for breast cancer: considerations for development of an improved risk prediction model. Endocr Relat Cancer 2007; 14(2): 169-87.
  • 5. Dieudonne MN, Bussiere M, Dos Santos E, Leneveu MC, Giudicelli Y, Pecquery R. Adiponectin mediates antiproliferative and apoptotic responses in human MCF7 breast cancer cells. Biochem Biophys Res Commun 2006; 345(1): 271-9.
  • 6. Tatemoto K, Hosoya M, Habata Y, Fujii R, Kakegawa T, Zou MX, Kawamata Y, Fukusumi S, Hinuma S, Kitada C, Kurokawa T, Onda H, Fujino M. Isolation and characterization of a novel endogenous peptide ligand for the human APJ receptor. Biochemical and Biophysical Research Communications 1998; 251(2): 471-476.
  • 7. Hinuma S, Onda H, Fujino M. The quest for novel bioactive peptides utilizing orphan seventransmembrane-domain receptors. J Mol Med (Berl) 1999; 77(6): 495-504.
  • 8. Todisco A, Campbell V, Dickinson CJ, DelValle J, Yamada T. Molecular basis for somatostatin action: inhibition of c-fos expression and AP-1 binding. Am J Physiol 1994; 267(2 Pt 1): G245-53.
  • 9. Hosoya M, Kawamata Y, Fukusumi S, Fujii R, Habata Y, Hinuma S, Kitada C, Honda S, Kurokawa T, Onda H, Nishimura O, Fujino M. Molecular and functional characteristics of APJ. Tissue distribution of mRNA and interaction with the endogenous ligand apelin. J Biol Chem 2000; 275(28): 21061-7.
  • 10. Kawamata Y, Habata Y, Fukusumi S, Hosoya M, Fujii R, Hinuma S, Nishizawa N, Kitada C, Onda H, Nishimura O, Fujino M. Molecular properties of apelin: tissue distribution and receptor binding. Biochim Biophys Acta 2001; 1538(2-3): 162-71.
  • 11. Habata Y, Fujii R, Hosoya M, Fukusumi S, Kawamata Y, Hinuma S, Kitada C, Nishizawa N, Murosaki S, Kurokawa T, Onda H, Tatemoto K, Fujino M. Apelin, the natural ligand of the orphan receptor APJ, is abundantly secreted in the colostrum. Biochimica et Biophysica Acta (BBA) - Molecular Cell Research 1999; 1452(1): 25-35.
  • 12. Wang G, Anini Y, Wei W, Qi X, O’Carroll A-M, Mochizuki T, Wang H-Q, Hellmich MR, Englander EW, Greeley GH. Apelin, a New Enteric Peptide: Localization in the Gastrointestinal Tract, Ontogeny, and Stimulation of Gastric Cell Proliferation and of Cholecystokinin Secretion. Endocrinology 2004; 145(3): 1342-1348.
  • 13. Wang G, Qi X, Wei W, Englander EW, Greeley GH, Jr. Characterization of the 5'-regulatory regions of the rat and human apelin genes and regulation of breast apelin by USF. FASEB J 2006; 20(14): 2639- 41.
  • 14. Wang Z, Greeley GH, Jr., Qiu S. Immunohistochemical localization of apelin in human normal breast and breast carcinoma. J Mol Histol 2008; 39(1): 121-4.
  • 15. Denizot F, Lang R. Rapid colorimetric assay for cell growth and survival: Modifications to the tetrazolium dye procedure giving improved sensitivity and reliability. Journal of Immunological Methods 1986; 89(2): 271-277.
  • 16. Horakova K, Sovcikova A, Seemannova Z, Syrova D, Busanyova K, Drobna Z, Ferencik M. Detection of drug-induced, superoxide-mediated cell damage and its prevention by antioxidants. Free Radic Biol Med 2001; 30(6): 650-64.
  • 17. Mosmann T. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods 1983; 65(1- 2): 55-63.
  • 18. Ray A. Adipokine leptin in obesity-related pathology of breast cancer. J Biosci 2012; 37(2): 289-94.
  • 19. Yaşartürk Ü, Altıntaş A. Meme Tümörlü Köpeklerde Serum 17β-estradiol Kolesterol ve Trigliserid Düzeylerinin Klinik Önemi. F.Ü.Sağ.Bil.Vet.Derg. 2010; 24(3): 157-161.
  • 20. Henderson BE, Ross R, Bernstein L. Estrogens as a Cause of Human Cancer: The Richard and Hinda Rosenthal Foundation Award Lecture. Cancer Research 1988; 48(2): 246-253
  • 21. Carlstrom K. Influence of intratumoral estradiol biosynthesis on estrogen receptors. Recent Results Cancer Res 1984; 91: 145-9.
  • 22. Osborne CK. Tamoxifen in the treatment of breast cancer. N Engl J Med 1998; 339(22): 1609-18.
  • 23. Gimble JM. Adipose tissue-derived therapeutics. Expert Opin Biol Ther 2003; 3(5): 705-13.
  • 24. Wozniak SE, Gee LL, Wachtel MS, Frezza EE. Adipose tissue: the new endocrine organ? A review article. Dig Dis Sci 2009; 54(9): 1847-56.
  • 25. Liu Y, Song CY, Wu SS, Liang QH, Yuan LQ, Liao EY. Novel adipokines and bone metabolism. Int J Endocrinol 2013; 2013: 895045.
  • 26. Popkin BM. Understanding global nutrition dynamics as a step towards controlling cancer incidence. Nat Rev Cancer 2007; 7(1): 61-7.
  • 27. Zhang Y, Proenca R, Maffei M, Barone M, Leopold L, Friedman JM. Positional cloning of the mouse obese gene and its human homologue. Nature 1994; 372(6505): 425-32.
  • 28. Garofalo C, Surmacz E. Leptin and cancer. J Cell Physiol 2006; 207(1): 12-22.
  • 29. Mantzoros C, Petridou E, Dessypris N, Chavelas C, Dalamaga M, Alexe DM, Papadiamantis Y, Markopoulos C, Spanos E, Chrousos G, Trichopoulos D. Adiponectin and breast cancer risk. J Clin Endocrinol Metab 2004; 89(3): 1102-7.
  • 30. Miyoshi Y, Funahashi T, Kihara S, Taguchi T, Tamaki Y, Matsuzawa Y, Noguchi S. Association of serum adiponectin levels with breast cancer risk. Clin Cancer Res 2003; 9(15): 5699-704.
  • 31. Matsubara M, Maruoka S, Katayose S. Inverse relationship between plasma adiponectin and leptin concentrations in normal-weight and obese women. European Journal of Endocrinology 2002; 147(2): 173-180.
  • 32. Kim JG, Kim EO, Jeong BR, Min YJ, Park JW, Kim ES, Namgoong IS, Kim YI, Lee BJ. Visfatin stimulates proliferation of MCF-7 human breast cancer cells. Mol Cells 2010; 30(4): 341-5.
  • 33. Somasundar P, Yu AK, Vona-Davis L, McFadden DW. Differential effects of leptin on cancer in vitro. J Surg Res 2003; 113(1): 50-5.
  • 34. Catalano S, Mauro L, Marsico S, Giordano C, Rizza P, Rago V, Montanaro D, Maggiolini M, Panno ML, Ando S. Leptin induces, via ERK1/ERK2 signal, functional activation of estrogen receptor alpha in MCF-7 cells. J Biol Chem 2004; 279(19): 19908-15.
  • 35. Grossmann ME, Nkhata KJ, Mizuno NK, Ray A, Cleary MP. Effects of adiponectin on breast cancer cell growth and signaling. Br J Cancer 2008; 98(2): 370-9.
  • 36. Berta J, Kenessey I, Dobos J, Tovari J, Klepetko W, Jan Ankersmit H, Hegedus B, Renyi-Vamos F, Varga J, Lorincz Z, Paku S, Ostoros G, Rozsas A, Timar J, Dome B. Apelin expression in human non- small cell lung cancer: role in angiogenesis and prognosis. J Thorac Oncol 2010; 5(8): 1120-9.
  • 37. Heo K, Kim YH, Sung HJ, Li HY, Yoo CW, Kim JY, Park JY, Lee UL, Nam BH, Kim EO, Kim SY, Lee SH, Park JB, Choi SW. Hypoxia-induced upregulation of apelin is associated with a poor prognosis in oral squamous cell carcinoma patients. Oral Oncology 2012; 48(6): 500-506.
There are 37 citations in total.

Details

Primary Language Turkish
Journal Section Research Article
Authors

Ferda Koyunoğlu This is me

Suat Tekin This is me

Vahit Konar This is me

Süleyman Sandal This is me

Publication Date April 1, 2013
Published in Issue Year 2013 Volume: 2 Issue: 1

Cite

APA Koyunoğlu, F., Tekin, S., Konar, V., Sandal, S. (2013). İnsan Meme Kanseri Hücre Serileri MCF-7 Üzerine Apelin-13’ün Etkilerinin Araştırılması: In Vitro Bir Çalışma. Annals of Health Sciences Research, 2(1), 23-28.
AMA Koyunoğlu F, Tekin S, Konar V, Sandal S. İnsan Meme Kanseri Hücre Serileri MCF-7 Üzerine Apelin-13’ün Etkilerinin Araştırılması: In Vitro Bir Çalışma. Ann Health Sci Res. April 2013;2(1):23-28.
Chicago Koyunoğlu, Ferda, Suat Tekin, Vahit Konar, and Süleyman Sandal. “İnsan Meme Kanseri Hücre Serileri MCF-7 Üzerine Apelin-13’ün Etkilerinin Araştırılması: In Vitro Bir Çalışma”. Annals of Health Sciences Research 2, no. 1 (April 2013): 23-28.
EndNote Koyunoğlu F, Tekin S, Konar V, Sandal S (April 1, 2013) İnsan Meme Kanseri Hücre Serileri MCF-7 Üzerine Apelin-13’ün Etkilerinin Araştırılması: In Vitro Bir Çalışma. Annals of Health Sciences Research 2 1 23–28.
IEEE F. Koyunoğlu, S. Tekin, V. Konar, and S. Sandal, “İnsan Meme Kanseri Hücre Serileri MCF-7 Üzerine Apelin-13’ün Etkilerinin Araştırılması: In Vitro Bir Çalışma”, Ann Health Sci Res, vol. 2, no. 1, pp. 23–28, 2013.
ISNAD Koyunoğlu, Ferda et al. “İnsan Meme Kanseri Hücre Serileri MCF-7 Üzerine Apelin-13’ün Etkilerinin Araştırılması: In Vitro Bir Çalışma”. Annals of Health Sciences Research 2/1 (April 2013), 23-28.
JAMA Koyunoğlu F, Tekin S, Konar V, Sandal S. İnsan Meme Kanseri Hücre Serileri MCF-7 Üzerine Apelin-13’ün Etkilerinin Araştırılması: In Vitro Bir Çalışma. Ann Health Sci Res. 2013;2:23–28.
MLA Koyunoğlu, Ferda et al. “İnsan Meme Kanseri Hücre Serileri MCF-7 Üzerine Apelin-13’ün Etkilerinin Araştırılması: In Vitro Bir Çalışma”. Annals of Health Sciences Research, vol. 2, no. 1, 2013, pp. 23-28.
Vancouver Koyunoğlu F, Tekin S, Konar V, Sandal S. İnsan Meme Kanseri Hücre Serileri MCF-7 Üzerine Apelin-13’ün Etkilerinin Araştırılması: In Vitro Bir Çalışma. Ann Health Sci Res. 2013;2(1):23-8.