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Siyah üzüm ekstresinin meme kanseri hücrelerinde MMP-9 gen ekspresyonuna etkisi

Yıl 2020, Cilt: 13 Sayı: 3, 194 - 199, 15.12.2020
https://doi.org/10.46309/biodicon.2020.824105

Öz

Meme kanseri sağ kalım oranındaki düşüş ve tedavisindeki başarısızlığın en önemli etkenleri arasında metastaz görülmektedir. Meme kanseri metastazının moleküler yolaklarının aydınlatılması büyük bir öneme sahiptir. Son yıllarda yapılan araştırmalar, bitkilerde bulunan polifenolik bileşiklerin anti-invaziv ve anti-metastatik yeteneklerine sahip olduğunu göstermektedir. Bol miktarda polifenol içeren siyah üzüm ekstresinin meme kanseri ve metastazı üzerindeki etkisi ve moleküler mekanizması henüz tam olarak bilinmemektedir. Çalışmamızda, insan meme kanseri hücre dizisine uygulanan siyah üzüm ektresinin hücre canlılığı ve adezyonuna etkisi ile metastazda rolü olabileceği düşünülen MMP-9 gen ekspresyonuna etkisinin belirlenmesi amaçlanmıştır. MCF-7 meme kanser hücre dizilerinde tripan blue yöntemi ile hücre canlılığı, XTT yöntemi ile hücre adezyonu ve qRT-PCR ile MMP-9 gen ekspresyonu belirlenmiştir. Çalışmamızda, siyah üzüm ekstresinin MMP-9 gen ekspresyonunu, hücre canlılığını ve adezyonunu (p>0.05) azalttığı bulunmuştur. Sonuç olarak polifenoller gibi doğal kanser önleyici ajanların kanserin oluşmasını ve yayılmasını önleyebileceği fikri desteklenmiştir. Bununla birlikte polifenollerin etkilediği moleküler mekanizmaların aydınlatılabilmesi için ileri çalışmalara ihtiyaç vardır.

Kaynakça

  • [1] Kleiner, D. E., & Stetler-Stevenson, W. G. (1999). Matrix metalloproteinases and metastasis. Cancer Chemotherapy and Pharmacology, 43(1), S42–S51.
  • [2] Klein, T., & Bischoff, R. (2011). Physiology and pathophysiology of matrix metalloproteases. Amino Acids, 41(2), 271–290.
  • [3] Nagase, H., Visse, R., & Murphy, G. (2006). Structure and function of matrix metalloproteinases and TIMPs. Cardiovascular Research, 69(3), 562–573.
  • [4] Kessenbrock, K., Plaks, V., & Werb, Z. (2010). Matrix metalloproteinases: regulators of the tumor microenvironment. Cell, 141(1), 52–67.
  • [5] Gialeli, C., Theocharis, A. D., & Karamanos, N. K. (2011). Roles of matrix metalloproteinases in cancer progression and their pharmacological targeting. The FEBS Journal, 278(1), 16–27.
  • [6] Huang, H. (2018). Matrix metalloproteinase-9 (MMP-9) as a cancer biomarker and MMP-9 biosensors: recent advances. Sensors, 18(10), 3249.
  • [7] Mehner, C., Hockla, A., Miller, E., Ran, S., Radisky, D. C., & Radisky, E. S. (2014). Tumor cell-produced matrix metalloproteinase 9 (MMP-9) drives malignant progression and metastasis of basal-like triple negative breast cancer. Oncotarget, 5(9), 2736.
  • [8] Pellikainen, J. M., Ropponen, K. M., Kataja, V. V, Kellokoski, J. K., Eskelinen, M. J., & Kosma, V.-M. (2004). Expression of matrix metalloproteinase (MMP)-2 and MMP-9 in breast cancer with a special reference to activator protein-2, HER2, and prognosis. Clinical Cancer Research, 10(22), 7621–7628.
  • [9] Vizoso, F. J., Gonzalez, L. O., Corte, M. D., Rodriguez, J. C., Vazquez, J., Lamelas, M. L., … Garcia-Muniz, J. L. (2007). Study of matrix metalloproteinases and their inhibitors in breast cancer. British Journal of Cancer, 96(6), 903.
  • [10] Yousef, E. M., Tahir, M. R., St-Pierre, Y., & Gaboury, L. A. (2014). MMP-9 expression varies according to molecular subtypes of breast cancer. BMC Cancer, 14(1), 609.
  • [11] Cao, D., Polyak, K., Halushka, M. K., Nassar, H., Kouprina, N., Iacobuzio-Donahue, C., … De Marzo, A. (2008). Serial analysis of gene expression of lobular carcinoma in situ identifies down regulation of claudin 4 and overexpression of matrix metalloproteinase 9. Breast Cancer Research, 10(5), R91.
  • [12] Roomi, M. W., Monterrey, J. C., Kalinovsky, T., Rath, M., & Niedzwiecki, A. (2009). Distinct patterns of matrix metalloproteinase-2 and-9 expression in normal human cell lines. Oncology Reports, 21(3), 821–826.
  • [13] Li, H., Qiu, Z., Li, F., & Wang, C. (2017). The relationship between MMP-2 and MMP-9 expression levels with breast cancer incidence and prognosis. Oncology Letters, 14(5), 5865–5870.
  • [14] Hao, L., Zhang, C., Qiu, Y., Wang, L., Luo, Y., Jin, M., … Zhang, Y. (2007). Recombination of CXCR4, VEGF, and MMP-9 predicting lymph node metastasis in human breast cancer. Cancer Letters, 253(1), 34–42.
  • [15] Wu, Z., Wu, Q., Yang, J., Wang, H., Ding, X., Yang, F., & Xu, X. (2008). Prognostic significance of MMP‐9 and TIMP‐1 serum and tissue expression in breast cancer. International Journal of Cancer, 122(9), 2050–2056.
  • [16] Manach, C., Scalbert, A., Morand, C., Rémésy, C., & Jiménez, L. (2004). Polyphenols: food sources and bioavailability. The American Journal of Clinical Nutrition, 79(5), 727–747. [17] Enoant. http://www.enoant.com.tr/
  • [18] Senel, S. N., Erdem, T. L., Ozcan, I., Uslu, E., & Oguz, N. (2018). Increase of free radical levels in the periodontal tissues of therapeutic dose radiation applied rats and potential protective effects of bioflavonoids and polyphenols (ENOANT®). Indian Journal of Animal Research, 52(12).
  • [19] Schmittgen, T. D., & Livak, K. J. (2008). Analyzing real-time PCR data by the comparative C T method. Nature Protocols, 3(6), 1101.
  • [20] Liu, R. H. (2004). Potential synergy of phytochemicals in cancer prevention: mechanism of action. The Journal of Nutrition, 134(12), 3479S–3485S.
  • [21] Varinska, L., Gal, P., Mojzisova, G., Mirossay, L., & Mojzis, J. (2015). Soy and breast cancer: focus on angiogenesis. International Journal of Molecular Sciences, 16(5), 11728–11749.
  • [22] Yang, C. S., Lambert, J. D., & Sang, S. (2009). Antioxidative and anti-carcinogenic activities of tea polyphenols. Archives of Toxicology, 83(1), 11–21.
  • [23] Ko, Y. S., Lee, W. S., Joo, Y. N., Choi, Y. H., Kim, G. S., Jung, J.-M., … Kim, H. J. (2015). Polyphenol mixtures of Euphorbia supina the inhibit invasion and metastasis of highly metastatic breast cancer MDA-MB-231 cells. Oncology Reports, 34(6), 3035–3042.
  • [24] Ko, Y. S., Lee, W. S., Panchanathan, R., Joo, Y. N., Choi, Y. H., Kim, G. S., … Kim, H. J. (2016). Polyphenols from artemisia annua L inhibit adhesion and EMT of highly metastatic breast cancer cells MDA‐MB‐231. Phytotherapy Research, 30(7), 1180–1188.
  • [25] Tang, F.-Y., Chiang, E.-P. I., & Sun, Y.-C. (2008). Resveratrol inhibits heregulin-β1-mediated matrix metalloproteinase-9 expression and cell invasion in human breast cancer cells. The Journal of Nutritional Biochemistry, 19(5), 287–294.
  • [26] Dinicola, S., Pasqualato, A., Cucina, A., Coluccia, P., Ferranti, F., Canipari, R., … Ricci, G. (2014). Grape seed extract suppresses MDA-MB231 breast cancer cell migration and invasion. European Journal of Nutrition, 53(2), 421–431.
  • [27] Leone, A., Longo, C., Gerardi, C., & Trosko, J. E. (2019). Pro-apoptotic effect of grape seed extract on MCF-7 involves transient increase of gap junction intercellular communication and Cx43 up-regulation: A mechanism of chemoprevention. International Journal of Molecular Sciences, 20(13), 3244.

Effect of black grape extract on MMP-9 gene expression in breast cancer cells

Yıl 2020, Cilt: 13 Sayı: 3, 194 - 199, 15.12.2020
https://doi.org/10.46309/biodicon.2020.824105

Öz

Metastasis is among the most important factors in the decrease in breast cancer survival and treatment failure. It is of great importance to elucidate the molecular pathways of breast cancer metastasis. Recent research shows that polyphenolic compounds in plants have anti-invasive and anti-metastatic activities. Molecular mechanism of black grape extract including abundant polyphenols on breast cancer and metastasis are not yet fully known. In our study, it was aimed to determine the effect of black grape extract applied to human breast cancer cell line on cell viability and adhesion and on MMP-9 gene expression, which is thought to have a role in metastasis. In the study, cell viability by trypan blue method, cell adhesion with XTT method and MMP-9 gene expression by qRT-PCR were determined in MCF-7 breast cancer cell lines. In our study, it was found that black grape extract decreased MMP-9 gene expression, cell viability and adhesion (p> 0.05). The study results support the hypothesis that natural anti-cancer agents such as polyphenols can prevent cancer from occurring and spreading. However, further studies are needed to elucidate the molecular mechanisms of polyphenols.

Kaynakça

  • [1] Kleiner, D. E., & Stetler-Stevenson, W. G. (1999). Matrix metalloproteinases and metastasis. Cancer Chemotherapy and Pharmacology, 43(1), S42–S51.
  • [2] Klein, T., & Bischoff, R. (2011). Physiology and pathophysiology of matrix metalloproteases. Amino Acids, 41(2), 271–290.
  • [3] Nagase, H., Visse, R., & Murphy, G. (2006). Structure and function of matrix metalloproteinases and TIMPs. Cardiovascular Research, 69(3), 562–573.
  • [4] Kessenbrock, K., Plaks, V., & Werb, Z. (2010). Matrix metalloproteinases: regulators of the tumor microenvironment. Cell, 141(1), 52–67.
  • [5] Gialeli, C., Theocharis, A. D., & Karamanos, N. K. (2011). Roles of matrix metalloproteinases in cancer progression and their pharmacological targeting. The FEBS Journal, 278(1), 16–27.
  • [6] Huang, H. (2018). Matrix metalloproteinase-9 (MMP-9) as a cancer biomarker and MMP-9 biosensors: recent advances. Sensors, 18(10), 3249.
  • [7] Mehner, C., Hockla, A., Miller, E., Ran, S., Radisky, D. C., & Radisky, E. S. (2014). Tumor cell-produced matrix metalloproteinase 9 (MMP-9) drives malignant progression and metastasis of basal-like triple negative breast cancer. Oncotarget, 5(9), 2736.
  • [8] Pellikainen, J. M., Ropponen, K. M., Kataja, V. V, Kellokoski, J. K., Eskelinen, M. J., & Kosma, V.-M. (2004). Expression of matrix metalloproteinase (MMP)-2 and MMP-9 in breast cancer with a special reference to activator protein-2, HER2, and prognosis. Clinical Cancer Research, 10(22), 7621–7628.
  • [9] Vizoso, F. J., Gonzalez, L. O., Corte, M. D., Rodriguez, J. C., Vazquez, J., Lamelas, M. L., … Garcia-Muniz, J. L. (2007). Study of matrix metalloproteinases and their inhibitors in breast cancer. British Journal of Cancer, 96(6), 903.
  • [10] Yousef, E. M., Tahir, M. R., St-Pierre, Y., & Gaboury, L. A. (2014). MMP-9 expression varies according to molecular subtypes of breast cancer. BMC Cancer, 14(1), 609.
  • [11] Cao, D., Polyak, K., Halushka, M. K., Nassar, H., Kouprina, N., Iacobuzio-Donahue, C., … De Marzo, A. (2008). Serial analysis of gene expression of lobular carcinoma in situ identifies down regulation of claudin 4 and overexpression of matrix metalloproteinase 9. Breast Cancer Research, 10(5), R91.
  • [12] Roomi, M. W., Monterrey, J. C., Kalinovsky, T., Rath, M., & Niedzwiecki, A. (2009). Distinct patterns of matrix metalloproteinase-2 and-9 expression in normal human cell lines. Oncology Reports, 21(3), 821–826.
  • [13] Li, H., Qiu, Z., Li, F., & Wang, C. (2017). The relationship between MMP-2 and MMP-9 expression levels with breast cancer incidence and prognosis. Oncology Letters, 14(5), 5865–5870.
  • [14] Hao, L., Zhang, C., Qiu, Y., Wang, L., Luo, Y., Jin, M., … Zhang, Y. (2007). Recombination of CXCR4, VEGF, and MMP-9 predicting lymph node metastasis in human breast cancer. Cancer Letters, 253(1), 34–42.
  • [15] Wu, Z., Wu, Q., Yang, J., Wang, H., Ding, X., Yang, F., & Xu, X. (2008). Prognostic significance of MMP‐9 and TIMP‐1 serum and tissue expression in breast cancer. International Journal of Cancer, 122(9), 2050–2056.
  • [16] Manach, C., Scalbert, A., Morand, C., Rémésy, C., & Jiménez, L. (2004). Polyphenols: food sources and bioavailability. The American Journal of Clinical Nutrition, 79(5), 727–747. [17] Enoant. http://www.enoant.com.tr/
  • [18] Senel, S. N., Erdem, T. L., Ozcan, I., Uslu, E., & Oguz, N. (2018). Increase of free radical levels in the periodontal tissues of therapeutic dose radiation applied rats and potential protective effects of bioflavonoids and polyphenols (ENOANT®). Indian Journal of Animal Research, 52(12).
  • [19] Schmittgen, T. D., & Livak, K. J. (2008). Analyzing real-time PCR data by the comparative C T method. Nature Protocols, 3(6), 1101.
  • [20] Liu, R. H. (2004). Potential synergy of phytochemicals in cancer prevention: mechanism of action. The Journal of Nutrition, 134(12), 3479S–3485S.
  • [21] Varinska, L., Gal, P., Mojzisova, G., Mirossay, L., & Mojzis, J. (2015). Soy and breast cancer: focus on angiogenesis. International Journal of Molecular Sciences, 16(5), 11728–11749.
  • [22] Yang, C. S., Lambert, J. D., & Sang, S. (2009). Antioxidative and anti-carcinogenic activities of tea polyphenols. Archives of Toxicology, 83(1), 11–21.
  • [23] Ko, Y. S., Lee, W. S., Joo, Y. N., Choi, Y. H., Kim, G. S., Jung, J.-M., … Kim, H. J. (2015). Polyphenol mixtures of Euphorbia supina the inhibit invasion and metastasis of highly metastatic breast cancer MDA-MB-231 cells. Oncology Reports, 34(6), 3035–3042.
  • [24] Ko, Y. S., Lee, W. S., Panchanathan, R., Joo, Y. N., Choi, Y. H., Kim, G. S., … Kim, H. J. (2016). Polyphenols from artemisia annua L inhibit adhesion and EMT of highly metastatic breast cancer cells MDA‐MB‐231. Phytotherapy Research, 30(7), 1180–1188.
  • [25] Tang, F.-Y., Chiang, E.-P. I., & Sun, Y.-C. (2008). Resveratrol inhibits heregulin-β1-mediated matrix metalloproteinase-9 expression and cell invasion in human breast cancer cells. The Journal of Nutritional Biochemistry, 19(5), 287–294.
  • [26] Dinicola, S., Pasqualato, A., Cucina, A., Coluccia, P., Ferranti, F., Canipari, R., … Ricci, G. (2014). Grape seed extract suppresses MDA-MB231 breast cancer cell migration and invasion. European Journal of Nutrition, 53(2), 421–431.
  • [27] Leone, A., Longo, C., Gerardi, C., & Trosko, J. E. (2019). Pro-apoptotic effect of grape seed extract on MCF-7 involves transient increase of gap junction intercellular communication and Cx43 up-regulation: A mechanism of chemoprevention. International Journal of Molecular Sciences, 20(13), 3244.
Toplam 26 adet kaynakça vardır.

Ayrıntılar

Birincil Dil Türkçe
Konular Biyokimya ve Hücre Biyolojisi (Diğer)
Bölüm Research Article
Yazarlar

Ahu Soyocak 0000-0003-0999-2774

Gülşah Koç 0000-0002-9678-5652

Yayımlanma Tarihi 15 Aralık 2020
Gönderilme Tarihi 10 Kasım 2020
Kabul Tarihi 9 Aralık 2020
Yayımlandığı Sayı Yıl 2020 Cilt: 13 Sayı: 3

Kaynak Göster

APA Soyocak, A., & Koç, G. (2020). Siyah üzüm ekstresinin meme kanseri hücrelerinde MMP-9 gen ekspresyonuna etkisi. Biological Diversity and Conservation, 13(3), 194-199. https://doi.org/10.46309/biodicon.2020.824105

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