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THE CYTOTOXIC EFFECTS OF PROTEASOME INHIBITOR MG132 ON 4T1 BREAST AND B16F10 MELANOMA CANCER CELLS

Year 2009, Issue: 019, 15 - 22, 15.08.2009

Abstract

Proteasome
is a proteolytic complex found in all eukaryotes, archaeabacteria and some
eubacteria. Increases in proteasome activity and subunits are commonly found in
many cancers. Proteasome inhibitors exhibits antitumor activities in a number
of cancer cell cultures by triggering apoptosis. Studies are currently
conducted  in many laboratories in order
to use proteasome inhibitors in cancer treatment. In this study, we
investigated the cytotoxic effects of proteasome inhibitor MG132 on 4T1 breast
and B16F10 melanoma cancer cells. It was determined that both cell lines are
sensitive to MG132 using morphologic criteria commonly found in apoptotic cells
and typan blue exclusion test. Results suggest that the proteasome inhibitors
may show effective anti-cancer effects against melonoma and breast cancers and
are therefore warranted to further investigation. 

References

  • 1] Hilt, W., Wolf, D.H. “Proteasomes: destruction as a programme”, Trends Biochem Sci., 21: 96-102 (1996).
  • [2] Hershko, A., Ciechanover, A. “The ubiquitin system”, Annu Rev Biochem., 67: 425-79 (1998).
  • [3] Yerlikaya, A. “Cellular functions of the 26S proteasome”, Turk J Biol., 28: 31-38 (2004).
  • [4] Mani, A., Gelmann, E.P. “The ubiquitin-proteasome pathway and its role in cancer”, J Clin Oncol., 23: 4776-89 (2005).
  • [5] Voges, D., Zwickl, P., Baumeister, W. “The 26S proteasome: a molecular machine designed for controlled proteolysis”, Annu Rev Biochem., 68: 1015-68 (1999).
  • [6] Adams, J. “The development of proteasome inhibitors as anticancer drugs”, Cancer Cell., 5: 417-21 (2004).
  • [7] Murakami, Y., Matsufuji, S., Kameji, T., Hayashi, S., Igarashi, K., Tamura, T., Tanaka, K., Ichihara, A. “Ornithine decarboxylase is degraded by the 26S proteasome without ubiquitination”, Nature, 360: 597-9 (1992).
  • [8] Pagano, M. “Cell cycle regulation by the ubiquitin pathway”, Faseb J., 11: 1067-75 (1997).
  • [9] He, H., Qi, X.M., Grossmann, J., Distelhorst, C.W. “c-Fos degradation by the proteasome. An early, Bcl-2-regulated step in apoptosis”, J Biol Chem., 273: 25015-9 (1998).
  • [10] Jentsch, S. “The ubiquitin-conjugation system”, Annu Rev Genet., 26: 179-207 (1992).
  • [11] Chau, V., Tobias, J.W., Bachmair, A., Marriott, D., Ecker, D.J., Gonda, D.K., Varshavsky, A. “A multiubiquitin chain is confined to specific lysine in a targeted short-lived protein”, Science, 243: 1576-83 (1989).
  • [12] Pickart, C.M. “Targeting of substrates to the 26S proteasome”, Faseb J., 11: 1055-66 (1997).
  • [13] Lee, D.H., Goldberg, A.L. “Proteasome inhibitors: valuable new tools for cell biologists”, Trends Cell Biol., 8: 397-403 (1998).
  • [14] Kerr, J.F., Wyllie, A.H., Currie, A.R. “Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics”, Br J Cancer, 26: 239-57 (1972).
  • [15] Edinger, A.L., Thompson, C.B. “Death by design: apoptosis, necrosis and autophagy”, Curr Opin Cell Biol., 16: 663-9 (2004).
  • [16] Clarke, P.G. “Developmental cell death: morphological diversity and multiple mechanisms”, Anat Embryol (Berl), 181: 195-213 (1990).
  • [17] Zhang, Q.Y., Jiang, M., Zhao, C.Q., Yu, M., Zhang, H., Ding, Y.J., Zhai, Y.G. “Apoptosis induced by one new podophyllotoxin glucoside in human carcinoma cells”, Toxicology, 212: 46-53 (2005).
  • [18] Drexler, H.C. “Activation of the cell death program by inhibition of proteasome function”, Proc Natl Acad Sci U S A., 94: 855-60 (1997).
  • [19] Yerlikaya, A., Erin, N. “Differential sensitivity of breast cancer and melanoma cells to proteasome inhibitor Velcade”, Int J Mol Med., 22: 817-23 (2008).
  • [20] Sadoul, R., Fernandez, P.A., Quiquerez, A.L., Martinou, I., Maki, M., Schroter, M., Becherer, J.D., Irmler, M., Tschopp, J., Martinou, J.C. “Involvement of the proteasome in the programmed cell death of NGF-deprived sympathetic neurons”, Embo J., 15: 3845-52 (1996).
  • [21] Lopes, U.G., Erhardt, P., Yao, R., Cooper, G.M. “p53-dependent induction of apoptosis by proteasome inhibitors”, J Biol Chem., 272: 12893-6 (1997).
  • [22] Chauhan, D., Hideshima, T., Mitsiades, C., Richardson, P., Anderson, K.C. “Proteasome inhibitor therapy in multiple myeloma”, Mol Cancer Ther., 4: 686-92 (2005).

PROTEOZOM İNHİBİTÖRÜ MG132’NİN 4T1 MEME VE B16F10 MELANOMA KANSER HÜCRELERİNDEKİ SİTOTOKSİK ETKİLERİ

Year 2009, Issue: 019, 15 - 22, 15.08.2009

Abstract

Proteozom,
tüm ökaryotlar, arkeobakteriler ve bazı bakterilerde bulunan proteolitik
aktiviteye sahip bir komplekstir. Çoğu kanserde proteozom aktivitesinde ve
alt-birimlerinde yükselmeler sıklıkla görülmektedir. Proteozom inhibitörleri
kanser hücre kültürlerinde apoptozisi uyararak anti-tümör aktivite
göstermektedirler. Proteozom inhibitörlerini kanser tedavisinde kullanmak için
çalışmalar birçok laboratuarda halen devam etmektedir. Bu çalışmada proteozom
inhibitörü MG132’nin 4T1 meme ve B16F10 melanoma kanser hücrelerindeki
sitotoksik etkileri araştırıldı. Apoptotik hücrelerde yaygın olarak kullanılan
morfolojik kriterler ve tripan mavisi testi ile her iki hücre kültürünün
MG132’ye hassas olduğunu belirledik. Bulgular, proteozom inhibitörlerinin
melanoma ve meme kanseri hücrelerine karşı anti-kanser etki
gösterebileceklerini ve bundan dolayı daha ileri düzeyde araştırılması
gerektiğini önermektedir.

References

  • 1] Hilt, W., Wolf, D.H. “Proteasomes: destruction as a programme”, Trends Biochem Sci., 21: 96-102 (1996).
  • [2] Hershko, A., Ciechanover, A. “The ubiquitin system”, Annu Rev Biochem., 67: 425-79 (1998).
  • [3] Yerlikaya, A. “Cellular functions of the 26S proteasome”, Turk J Biol., 28: 31-38 (2004).
  • [4] Mani, A., Gelmann, E.P. “The ubiquitin-proteasome pathway and its role in cancer”, J Clin Oncol., 23: 4776-89 (2005).
  • [5] Voges, D., Zwickl, P., Baumeister, W. “The 26S proteasome: a molecular machine designed for controlled proteolysis”, Annu Rev Biochem., 68: 1015-68 (1999).
  • [6] Adams, J. “The development of proteasome inhibitors as anticancer drugs”, Cancer Cell., 5: 417-21 (2004).
  • [7] Murakami, Y., Matsufuji, S., Kameji, T., Hayashi, S., Igarashi, K., Tamura, T., Tanaka, K., Ichihara, A. “Ornithine decarboxylase is degraded by the 26S proteasome without ubiquitination”, Nature, 360: 597-9 (1992).
  • [8] Pagano, M. “Cell cycle regulation by the ubiquitin pathway”, Faseb J., 11: 1067-75 (1997).
  • [9] He, H., Qi, X.M., Grossmann, J., Distelhorst, C.W. “c-Fos degradation by the proteasome. An early, Bcl-2-regulated step in apoptosis”, J Biol Chem., 273: 25015-9 (1998).
  • [10] Jentsch, S. “The ubiquitin-conjugation system”, Annu Rev Genet., 26: 179-207 (1992).
  • [11] Chau, V., Tobias, J.W., Bachmair, A., Marriott, D., Ecker, D.J., Gonda, D.K., Varshavsky, A. “A multiubiquitin chain is confined to specific lysine in a targeted short-lived protein”, Science, 243: 1576-83 (1989).
  • [12] Pickart, C.M. “Targeting of substrates to the 26S proteasome”, Faseb J., 11: 1055-66 (1997).
  • [13] Lee, D.H., Goldberg, A.L. “Proteasome inhibitors: valuable new tools for cell biologists”, Trends Cell Biol., 8: 397-403 (1998).
  • [14] Kerr, J.F., Wyllie, A.H., Currie, A.R. “Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics”, Br J Cancer, 26: 239-57 (1972).
  • [15] Edinger, A.L., Thompson, C.B. “Death by design: apoptosis, necrosis and autophagy”, Curr Opin Cell Biol., 16: 663-9 (2004).
  • [16] Clarke, P.G. “Developmental cell death: morphological diversity and multiple mechanisms”, Anat Embryol (Berl), 181: 195-213 (1990).
  • [17] Zhang, Q.Y., Jiang, M., Zhao, C.Q., Yu, M., Zhang, H., Ding, Y.J., Zhai, Y.G. “Apoptosis induced by one new podophyllotoxin glucoside in human carcinoma cells”, Toxicology, 212: 46-53 (2005).
  • [18] Drexler, H.C. “Activation of the cell death program by inhibition of proteasome function”, Proc Natl Acad Sci U S A., 94: 855-60 (1997).
  • [19] Yerlikaya, A., Erin, N. “Differential sensitivity of breast cancer and melanoma cells to proteasome inhibitor Velcade”, Int J Mol Med., 22: 817-23 (2008).
  • [20] Sadoul, R., Fernandez, P.A., Quiquerez, A.L., Martinou, I., Maki, M., Schroter, M., Becherer, J.D., Irmler, M., Tschopp, J., Martinou, J.C. “Involvement of the proteasome in the programmed cell death of NGF-deprived sympathetic neurons”, Embo J., 15: 3845-52 (1996).
  • [21] Lopes, U.G., Erhardt, P., Yao, R., Cooper, G.M. “p53-dependent induction of apoptosis by proteasome inhibitors”, J Biol Chem., 272: 12893-6 (1997).
  • [22] Chauhan, D., Hideshima, T., Mitsiades, C., Richardson, P., Anderson, K.C. “Proteasome inhibitor therapy in multiple myeloma”, Mol Cancer Ther., 4: 686-92 (2005).
There are 22 citations in total.

Details

Primary Language Turkish
Subjects Engineering
Journal Section Articles
Authors

Azmi Yerlikaya This is me

Harun Dokudur This is me

Semih Şeker This is me

Publication Date August 15, 2009
Published in Issue Year 2009 Issue: 019

Cite

APA Yerlikaya, A., Dokudur, H., & Şeker, S. (2009). PROTEOZOM İNHİBİTÖRÜ MG132’NİN 4T1 MEME VE B16F10 MELANOMA KANSER HÜCRELERİNDEKİ SİTOTOKSİK ETKİLERİ. Journal of Science and Technology of Dumlupınar University(019), 15-22.

HAZİRAN 2020'den itibaren Journal of Scientific Reports-A adı altında ingilizce olarak yayın hayatına devam edecektir.