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A POTENTIAL TARGET FOR DEVOLOPING BROAD SPECTRUM ANTICANCERS: HEXOKINASE-II

Yıl 2022, Cilt: 46 Sayı: 1, 182 - 192, 29.01.2022

Mevlüt Akdağ Azime Berna Özçelik

https://doi.org/10.33483/jfpau.978805

Öz

Objective: As a result of increased need of glucose, reprogramming the metabolic pathways related to respiration is a significant change in cancer cells which differs them from normal cells and this change is known as “Warburg Phenomenon” because firstly reported by Otto Warburg in 1920s. Increased glycolysis in cancer cells makes glycolysis pathway an important target for cancer tratment. Hexokinase (HK), first and one of the rate limiting steps of glycolitic pathway, is an important target through this perspective since the prominent phenotype in cancer cells is HK-II, this makes the development of new therapies against this isozyme possible. Using medicinal chemistry approaches new inhibitors can be designed by determining the heterocycles and functional groups providing selectivity against this isozyme.
Result and Discussion: Selective therapies against HK-II are based on inhibition, regulation, and expression of this enzyme. Small molecules targeting HK-II provide a basis for developing novel molecules. The discovery of selective inhibitors of HK-II is a promising progress for using selective and wide spectrum agents against cancer in the future cancer therapy.

Anahtar Kelimeler

Cancer chemotherapy glycolysis hexokinase Warburg Effect

Kaynakça

  • Pirastehzad, A., Taghizadeh, A., Jamshidi, A. A. (2020). The formation of cancer stem cells in EMT6/Ro tumor: Hybrid modeling within its micro-environment. Informatics in Medicine Unlocked, 18, 100247.
  • Valkenburg, K. C., de Groot, A. E., Pienta, K. J. (2018). Targeting the tumour stroma to improve cancer therapy. Nature reviews Clinical oncology, 15(6), 366-381.
  • Hemalatha, T., UmaMaheswari, T., Krithiga, G., Sankaranarayanan, P., Puvanakrishnan, R. (2013). Enzymes in clinical medicine: an overview.
  • Bobrovnikova-Marjon, E., Hurov, J. B. (2014). Targeting metabolic changes in cancer: novel therapeutic approaches. Annual review of medicine, 65.
  • Warburg, O., Wind, F., Negelein, E. (1927). The metabolism of tumors in the body. The Journal of general physiology, 8(6), 519-530.
  • Warburg, O. (1956). On the origin of cancer cells. Science, 123(3191), 309-314.
  • Hundshammer, C., Braeuer, M., Müller, C. A., Hansen, A. E., Schillmaier, M., Düwel, S., Feuerecker, B., Glaser, S.J., Haase, A., Weicherd, W., Steiger, K., Cabello, J., Schilling, F., Hövener, J., Kjaer, A., Nekolla, S.G., Schwaiger, M. (2018). Simultaneous characterization of tumor cellularity and the Warburg effect with PET, MRI and hyperpolarized 13C-MRSI. Theranostics, 8(17), 4765.
  • Mathupala, S. P., Ko, Y. A., Pedersen, P. L. (2006). Hexokinase II: cancer's double-edged sword acting as both facilitator and gatekeeper of malignancy when bound to mitochondria. Oncogene, 25(34), 4777-4786.
  • Lehninger, A. L., Nelson, D. L., Cox, M. M. (2005). Lehninger principles of biochemistry. Macmillan.
  • Courtnay, R., Ngo, D. C., Malik, N., Ververis, K., Tortorella, S. M., Karagiannis, T. C. (2015). Cancer metabolism and the Warburg effect: the role of HIF-1 and PI3K. Molecular biology reports, 42(4), 841-851.
  • Kaelin Jr, W. G., Ratcliffe, P. J. (2008). Oxygen sensing by metazoans: the central role of the HIF hydroxylase pathway. Molecular cell, 30(4), 393-402.
  • Vander Heiden, M. G., Cantley, L. C., Thompson, C. B. (2009). Understanding the Warburg effect: the metabolic requirements of cell proliferation. science, 324(5930), 1029-1033.
  • Gill, K. S., Fernandes, P., O'Donovan, T. R., McKenna, S. L., Doddakula, K. K., Power, D. G., Soden, D.M., Forde, P. F. (2016). Glycolysis inhibition as a cancer treatment and its role in an anti-tumour immune response. Biochimica et Biophysica Acta (BBA)-Reviews on Cancer, 1866(1), 87-105.
  • Roberts, D. J., Miyamoto, S. (2015). Hexokinase II integrates energy metabolism and cellular protection: Akting on mitochondria and TORCing to autophagy. Cell Death & Differentiation, 22(2), 248-257.
  • Miyamoto, S., Murphy, A. N., Brown, J. H. (2008). Akt mediates mitochondrial protection in cardiomyocytes through phosphorylation of mitochondrial hexokinase-II. Cell Death & Differentiation, 15(3), 521-529.
  • Fruehauf, J. P., Meyskens, F. L. (2007). Reactive oxygen species: a breath of life or death?. Clinical Cancer Research, 13(3), 789-794.
  • Tan, V. P., Miyamoto, S. (2015). HK2/hexokinase-II integrates glycolysis and autophagy to confer cellular protection. Autophagy, 11(6), 963-964.
  • Min, J. W., Kim, K. I., Kim, H. A., Kim, E. K., Noh, W. C., Jeon, H. B., Cho D.H., Oh J.S., Park I.C., Hwang S.G., Kim, J. S. (2013). INPP4B-mediated tumor resistance is associated with modulation of glucose metabolism via hexokinase 2 regulation in laryngeal cancer cells. Biochemical and biophysical research communications, 440(1), 137-142.
  • Lin, H., Zeng, J., Xie, R., Schulz, M. J., Tedesco, R., Qu, J., Erhard, K.F., Mack, J.F.,Raha, K., Rendina, A.R., Szewczuk,L.M., Kratz, P.M., Jurewicz,A.J., Cecconie,T., Martens S., McDevitt, P.J., Martin,J.D., Chen, S.B., Jiang,Y., Nickels,L., Schwartz,B.J., Smallwood,A.,Zhao, B., Campobasso, N., Qian,Y., Briand,J., Rominger, C.M.,Oleykowski, C., Hardwicke M.A., Luengo, J. I. (2016). Discovery of a novel 2, 6-disubstituted glucosamine series of potent and selective hexokinase 2 inhibitors. ACS medicinal chemistry letters, 7(3), 217-222.
  • Hu, J. W., Sun, P., Zhang, D. X., Xiong, W. J., Mi, J. (2014). Hexokinase 2 regulates G1/S checkpoint through CDK2 in cancer-associated fibroblasts. Cellular signalling, 26(10), 2210-2216.
  • Fang, R., Xiao, T., Fang, Z., Sun, Y., Li, F., Gao, Y., Feng, Y., Li, L., Wang., Y., Liu, X., Chen, H., Liu, X., Ji, H. (2012). MicroRNA-143 (miR-143) regulates cancer glycolysis via targeting hexokinase 2 gene. Journal of Biological Chemistry, 287(27), 23227-23235.
  • Shoshan, M. C. (2012). 3-Bromopyruvate: targets and outcomes. Journal of bioenergetics and biomembranes, 44(1), 7-15.
  • Queirós, O., Preto, A., Pacheco, A., Pinheiro, C., Azevedo-Silva, J., Moreira, R., Pedro, M.,Ko, Y.H., Pendersen, P.L., Baltazar, F., Casal, M. (2012). Butyrate activates the monocarboxylate transporter MCT4 expression in breast cancer cells and enhances the antitumor activity of 3-bromopyruvate. Journal of bioenergetics and biomembranes, 44(1), 141-153.
  • Chen, Z., Zhang, H., Lu, W., Huang, P. (2009). Role of mitochondria-associated hexokinase II in cancer cell death induced by 3-bromopyruvate. Biochimica et Biophysica Acta (BBA)-Bioenergetics, 1787(5), 553-560.
  • Ko, Y. H., Pedersen, P. L., Geschwind, J. F. (2001). Glucose catabolism in the rabbit VX2 tumor model for liver cancer: characterization and targeting hexokinase. Cancer letters, 173(1), 83-91.
  • Ko, Y. H., Smith, B. L., Wang, Y., Pomper, M. G., Rini, D. A., Torbenson, M. S., Hullihen J., Pedersen, P. L. (2004). Advanced cancers: eradication in all cases using 3-bromopyruvate therapy to deplete ATP. Biochemical and biophysical research communications, 324(1), 269-275.
  • Pruss, M., Dwucet, A., Tanriover, M., Hlavac, M., Kast, R. E., Debatin, K. M., Wirtz, C.R., Halatsch, M., Siegelin, M.D., Westhoff, M., Karpel-Massler, G. (2020). Dual metabolic reprogramming by ONC201/TIC10 and 2-Deoxyglucose induces energy depletion and synergistic anti-cancer activity in glioblastoma. British journal of cancer, 122(8), 1146-1157.
  • Cheng, G., Zielonka, J., Dranka, B. P., McAllister, D., Mackinnon, A. C., Joseph, J., Kalyanaraman, B. (2012). Mitochondria-targeted drugs synergize with 2-deoxyglucose to trigger breast cancer cell death. Cancer research, 72(10), 2634-2644.
  • Nath, K., Guo, L., Nancolas, B., Nelson, D. S., Shestov, A. A., Lee, S. C., Roman, J., Zhou, R., Leeper, D.P., Halestrap, A.P., Blair, I.A., Glickson, J. D. (2016). Mechanism of antineoplastic activity of lonidamine. Biochimica et Biophysica Acta (BBA)-Reviews on Cancer, 1866(2), 151-162.
  • Chen, H., Chen, F., Hu, W., Gou, S. (2018). Effective platinum (IV) prodrugs conjugated with lonidamine as a functional group working on the mitochondria. Journal of inorganic biochemistry, 180, 119-128.
  • Li, W., Zheng, M., Wu, S., Gao, S., Yang, M., Li, Z., Min, Q., Sun, W., Chen, L., Xiang, G., Li, H. (2017). Benserazide, a dopadecarboxylase inhibitor, suppresses tumor growth by targeting hexokinase 2. Journal of Experimental & Clinical Cancer Research, 36(1), 1-12.
  • Salani, B., Marini, C., Del Rio, A., Ravera, S., Massollo, M., Orengo, A. M., Amaro, A., Passalacqua, M., Maffioli, S., Pfeffer, U., Cordera, R., Maggi, D., Sambuceti, G. (2013). Metformin impairs glucose consumption and survival in Calu-1 cells by direct inhibition of hexokinase-II. Scientific reports, 3(1), 1-8.
  • Adinolfi, B., Carpi, S., Romanini, A., Da Pozzo, E., Castagna, M., Costa, B.,Martini, C., Olensen, S., Schmitt, N., Breschi, M., C., Nieri, P., Fogli, S. (2015). Analysis of the antitumor activity of clotrimazole on A375 human melanoma cells. Anticancer research, 35(7), 3781-3786.
  • Goldin, N., Arzoine, L., Heyfets, A., Israelson, A., Zaslavsky, Z., Bravman, T., Bronner, V., Notcovich, A., Shoshan-Barmatz, V., Flescher, E. (2008). Methyl jasmonate binds to and detaches mitochondria-bound hexokinase. Oncogene, 27(34), 4636-4643.
  • Liu, Y., Li, M., Zhang, Y., Wu, C., Yang, K., Gao, S., Zheng, M., Li, X., Li, H., Chen, L. (2020). Structure based discovery of novel hexokinase 2 inhibitors. Bioorganic chemistry, 96, 103609. [CrossRef]
  • Zheng, M., Wu, C., Yang, K., Yang, Y., Liu, Y., Gao, S.,Wang, Q., Li, C., Chen, L., Li, H. (2021). Novel selective hexokinase 2 inhibitor Benitrobenrazide blocks cancer cells growth by targeting glycolysis. Pharmacological Research, 164, 105367.
  • Li, W., Gao, F., Ma, X., Wang, R., Dong, X., Wang, W. (2017). Deguelin inhibits non-small cell lung cancer via down-regulating Hexokinases II-mediated glycolysis. Oncotarget, 8(20), 32586.
  • Li, W., Ma, X., Li, N., Liu, H., Dong, Q., Zhang, J., Yang, C., Liu, Y., Liang, Q., Zhang, S., Xu, C.,Song, W., Tan, S., Rong, P., Wang, W. (2016). Resveratrol inhibits Hexokinases II mediated glycolysis in non-small cell lung cancer via targeting Akt signaling pathway. Experimental cell research, 349(2), 320-327.
  • Xu, D., Jin, J., Yu, H., Zhao, Z., Ma, D., Zhang, C., Jiang, H. (2017). Chrysin inhibited tumor glycolysis and induced apoptosis in hepatocellular carcinoma by targeting hexokinase-2. Journal of Experimental & Clinical Cancer Research, 36(1), 1-11.
  • Tao, L., Wei, L., Liu, Y., Ding, Y., Liu, X., Zhang, X., Wang, X., Yao, Y., Lu, J., Wang, Q., Hu, R. (2017). Gen-27, a newly synthesized flavonoid, inhibits glycolysis and induces cell apoptosis via suppression of hexokinase II in human breast cancer cells. Biochemical pharmacology, 125, 12-25.
  • Yao, J., Liu, J., Zhao, W. (2018). By blocking hexokinase-2 phosphorylation, limonin suppresses tumor glycolysis and induces cell apoptosis in hepatocellular carcinoma. OncoTargets and therapy, 11, 3793.

GENİŞ SPEKTRUMLU ANTİKANSER BİLEŞİKLER GELİŞTİRMEYE YÖNELİK POTANSİYEL BİR HEDEF: HEKSOKİNAZ-II

Yıl 2022, Cilt: 46 Sayı: 1, 182 - 192, 29.01.2022

Mevlüt Akdağ Azime Berna Özçelik

https://doi.org/10.33483/jfpau.978805

Öz

Amaç: Kanser hücrelerinin glikoza duydukları ihtiyaç sonucu solunumla ilgili metabolik yolaklarını yeniden düzenlemesi, kanser hücrelerini normal hücrelerden ayıran önemli değişimlerden biridir ve bu değişim ilk olarak 1920’li yıllarda Otto Warburg tarafından rapor edildiği için “Warburg Fenomeni” olarak bilinir. Kanser hücrelerindeki artmış glikoliz, bu yolağı önemli bir kanser hedefi haline getirir. Glikolizin ilk ve hız kısıtlayıcı basamaklarından biri olan Heksokinaz (HK) enzimi bu açıdan önemli bir hedeftir ve kanser hücrelerinde karşımıza çıkan HK-II’nin baskın olduğu fenotip bu izozime yönelik tedavilerin geliştirilmesini mümkün kılar. Medisinal kimya yaklaşımları kullanılarak bu izozime karşı selektivite sağlayan heterosiklik yapılar ve fonksiyonel gruplar belirlenerek yeni inhibitörler dizayn edilebilir.
Sonuç ve Tartışma: HK-II’ye yönelik selektif tedaviler enzimin inhibisyonunu, regülasyonunu ve ekspresyonunu temel alır. HK-II’yi hedef alan küçük moleküller yeni moleküllerin keşfi için bir temel oluşturmaktadır. HK-II’ye selektif inhibitörlerin keşfi, kansere yönelik spesifik ve geniş spektrumlu ajanların gelecekte tedavide yer alabilmesi bakımından umut verici bir gelişmedir.

Anahtar Kelimeler

Glikoliz heksokinaz kanser kemoterapi Warburg Etkisi

Kaynakça

  • Pirastehzad, A., Taghizadeh, A., Jamshidi, A. A. (2020). The formation of cancer stem cells in EMT6/Ro tumor: Hybrid modeling within its micro-environment. Informatics in Medicine Unlocked, 18, 100247.
  • Valkenburg, K. C., de Groot, A. E., Pienta, K. J. (2018). Targeting the tumour stroma to improve cancer therapy. Nature reviews Clinical oncology, 15(6), 366-381.
  • Hemalatha, T., UmaMaheswari, T., Krithiga, G., Sankaranarayanan, P., Puvanakrishnan, R. (2013). Enzymes in clinical medicine: an overview.
  • Bobrovnikova-Marjon, E., Hurov, J. B. (2014). Targeting metabolic changes in cancer: novel therapeutic approaches. Annual review of medicine, 65.
  • Warburg, O., Wind, F., Negelein, E. (1927). The metabolism of tumors in the body. The Journal of general physiology, 8(6), 519-530.
  • Warburg, O. (1956). On the origin of cancer cells. Science, 123(3191), 309-314.
  • Hundshammer, C., Braeuer, M., Müller, C. A., Hansen, A. E., Schillmaier, M., Düwel, S., Feuerecker, B., Glaser, S.J., Haase, A., Weicherd, W., Steiger, K., Cabello, J., Schilling, F., Hövener, J., Kjaer, A., Nekolla, S.G., Schwaiger, M. (2018). Simultaneous characterization of tumor cellularity and the Warburg effect with PET, MRI and hyperpolarized 13C-MRSI. Theranostics, 8(17), 4765.
  • Mathupala, S. P., Ko, Y. A., Pedersen, P. L. (2006). Hexokinase II: cancer's double-edged sword acting as both facilitator and gatekeeper of malignancy when bound to mitochondria. Oncogene, 25(34), 4777-4786.
  • Lehninger, A. L., Nelson, D. L., Cox, M. M. (2005). Lehninger principles of biochemistry. Macmillan.
  • Courtnay, R., Ngo, D. C., Malik, N., Ververis, K., Tortorella, S. M., Karagiannis, T. C. (2015). Cancer metabolism and the Warburg effect: the role of HIF-1 and PI3K. Molecular biology reports, 42(4), 841-851.
  • Kaelin Jr, W. G., Ratcliffe, P. J. (2008). Oxygen sensing by metazoans: the central role of the HIF hydroxylase pathway. Molecular cell, 30(4), 393-402.
  • Vander Heiden, M. G., Cantley, L. C., Thompson, C. B. (2009). Understanding the Warburg effect: the metabolic requirements of cell proliferation. science, 324(5930), 1029-1033.
  • Gill, K. S., Fernandes, P., O'Donovan, T. R., McKenna, S. L., Doddakula, K. K., Power, D. G., Soden, D.M., Forde, P. F. (2016). Glycolysis inhibition as a cancer treatment and its role in an anti-tumour immune response. Biochimica et Biophysica Acta (BBA)-Reviews on Cancer, 1866(1), 87-105.
  • Roberts, D. J., Miyamoto, S. (2015). Hexokinase II integrates energy metabolism and cellular protection: Akting on mitochondria and TORCing to autophagy. Cell Death & Differentiation, 22(2), 248-257.
  • Miyamoto, S., Murphy, A. N., Brown, J. H. (2008). Akt mediates mitochondrial protection in cardiomyocytes through phosphorylation of mitochondrial hexokinase-II. Cell Death & Differentiation, 15(3), 521-529.
  • Fruehauf, J. P., Meyskens, F. L. (2007). Reactive oxygen species: a breath of life or death?. Clinical Cancer Research, 13(3), 789-794.
  • Tan, V. P., Miyamoto, S. (2015). HK2/hexokinase-II integrates glycolysis and autophagy to confer cellular protection. Autophagy, 11(6), 963-964.
  • Min, J. W., Kim, K. I., Kim, H. A., Kim, E. K., Noh, W. C., Jeon, H. B., Cho D.H., Oh J.S., Park I.C., Hwang S.G., Kim, J. S. (2013). INPP4B-mediated tumor resistance is associated with modulation of glucose metabolism via hexokinase 2 regulation in laryngeal cancer cells. Biochemical and biophysical research communications, 440(1), 137-142.
  • Lin, H., Zeng, J., Xie, R., Schulz, M. J., Tedesco, R., Qu, J., Erhard, K.F., Mack, J.F.,Raha, K., Rendina, A.R., Szewczuk,L.M., Kratz, P.M., Jurewicz,A.J., Cecconie,T., Martens S., McDevitt, P.J., Martin,J.D., Chen, S.B., Jiang,Y., Nickels,L., Schwartz,B.J., Smallwood,A.,Zhao, B., Campobasso, N., Qian,Y., Briand,J., Rominger, C.M.,Oleykowski, C., Hardwicke M.A., Luengo, J. I. (2016). Discovery of a novel 2, 6-disubstituted glucosamine series of potent and selective hexokinase 2 inhibitors. ACS medicinal chemistry letters, 7(3), 217-222.
  • Hu, J. W., Sun, P., Zhang, D. X., Xiong, W. J., Mi, J. (2014). Hexokinase 2 regulates G1/S checkpoint through CDK2 in cancer-associated fibroblasts. Cellular signalling, 26(10), 2210-2216.
  • Fang, R., Xiao, T., Fang, Z., Sun, Y., Li, F., Gao, Y., Feng, Y., Li, L., Wang., Y., Liu, X., Chen, H., Liu, X., Ji, H. (2012). MicroRNA-143 (miR-143) regulates cancer glycolysis via targeting hexokinase 2 gene. Journal of Biological Chemistry, 287(27), 23227-23235.
  • Shoshan, M. C. (2012). 3-Bromopyruvate: targets and outcomes. Journal of bioenergetics and biomembranes, 44(1), 7-15.
  • Queirós, O., Preto, A., Pacheco, A., Pinheiro, C., Azevedo-Silva, J., Moreira, R., Pedro, M.,Ko, Y.H., Pendersen, P.L., Baltazar, F., Casal, M. (2012). Butyrate activates the monocarboxylate transporter MCT4 expression in breast cancer cells and enhances the antitumor activity of 3-bromopyruvate. Journal of bioenergetics and biomembranes, 44(1), 141-153.
  • Chen, Z., Zhang, H., Lu, W., Huang, P. (2009). Role of mitochondria-associated hexokinase II in cancer cell death induced by 3-bromopyruvate. Biochimica et Biophysica Acta (BBA)-Bioenergetics, 1787(5), 553-560.
  • Ko, Y. H., Pedersen, P. L., Geschwind, J. F. (2001). Glucose catabolism in the rabbit VX2 tumor model for liver cancer: characterization and targeting hexokinase. Cancer letters, 173(1), 83-91.
  • Ko, Y. H., Smith, B. L., Wang, Y., Pomper, M. G., Rini, D. A., Torbenson, M. S., Hullihen J., Pedersen, P. L. (2004). Advanced cancers: eradication in all cases using 3-bromopyruvate therapy to deplete ATP. Biochemical and biophysical research communications, 324(1), 269-275.
  • Pruss, M., Dwucet, A., Tanriover, M., Hlavac, M., Kast, R. E., Debatin, K. M., Wirtz, C.R., Halatsch, M., Siegelin, M.D., Westhoff, M., Karpel-Massler, G. (2020). Dual metabolic reprogramming by ONC201/TIC10 and 2-Deoxyglucose induces energy depletion and synergistic anti-cancer activity in glioblastoma. British journal of cancer, 122(8), 1146-1157.
  • Cheng, G., Zielonka, J., Dranka, B. P., McAllister, D., Mackinnon, A. C., Joseph, J., Kalyanaraman, B. (2012). Mitochondria-targeted drugs synergize with 2-deoxyglucose to trigger breast cancer cell death. Cancer research, 72(10), 2634-2644.
  • Nath, K., Guo, L., Nancolas, B., Nelson, D. S., Shestov, A. A., Lee, S. C., Roman, J., Zhou, R., Leeper, D.P., Halestrap, A.P., Blair, I.A., Glickson, J. D. (2016). Mechanism of antineoplastic activity of lonidamine. Biochimica et Biophysica Acta (BBA)-Reviews on Cancer, 1866(2), 151-162.
  • Chen, H., Chen, F., Hu, W., Gou, S. (2018). Effective platinum (IV) prodrugs conjugated with lonidamine as a functional group working on the mitochondria. Journal of inorganic biochemistry, 180, 119-128.
  • Li, W., Zheng, M., Wu, S., Gao, S., Yang, M., Li, Z., Min, Q., Sun, W., Chen, L., Xiang, G., Li, H. (2017). Benserazide, a dopadecarboxylase inhibitor, suppresses tumor growth by targeting hexokinase 2. Journal of Experimental & Clinical Cancer Research, 36(1), 1-12.
  • Salani, B., Marini, C., Del Rio, A., Ravera, S., Massollo, M., Orengo, A. M., Amaro, A., Passalacqua, M., Maffioli, S., Pfeffer, U., Cordera, R., Maggi, D., Sambuceti, G. (2013). Metformin impairs glucose consumption and survival in Calu-1 cells by direct inhibition of hexokinase-II. Scientific reports, 3(1), 1-8.
  • Adinolfi, B., Carpi, S., Romanini, A., Da Pozzo, E., Castagna, M., Costa, B.,Martini, C., Olensen, S., Schmitt, N., Breschi, M., C., Nieri, P., Fogli, S. (2015). Analysis of the antitumor activity of clotrimazole on A375 human melanoma cells. Anticancer research, 35(7), 3781-3786.
  • Goldin, N., Arzoine, L., Heyfets, A., Israelson, A., Zaslavsky, Z., Bravman, T., Bronner, V., Notcovich, A., Shoshan-Barmatz, V., Flescher, E. (2008). Methyl jasmonate binds to and detaches mitochondria-bound hexokinase. Oncogene, 27(34), 4636-4643.
  • Liu, Y., Li, M., Zhang, Y., Wu, C., Yang, K., Gao, S., Zheng, M., Li, X., Li, H., Chen, L. (2020). Structure based discovery of novel hexokinase 2 inhibitors. Bioorganic chemistry, 96, 103609. [CrossRef]
  • Zheng, M., Wu, C., Yang, K., Yang, Y., Liu, Y., Gao, S.,Wang, Q., Li, C., Chen, L., Li, H. (2021). Novel selective hexokinase 2 inhibitor Benitrobenrazide blocks cancer cells growth by targeting glycolysis. Pharmacological Research, 164, 105367.
  • Li, W., Gao, F., Ma, X., Wang, R., Dong, X., Wang, W. (2017). Deguelin inhibits non-small cell lung cancer via down-regulating Hexokinases II-mediated glycolysis. Oncotarget, 8(20), 32586.
  • Li, W., Ma, X., Li, N., Liu, H., Dong, Q., Zhang, J., Yang, C., Liu, Y., Liang, Q., Zhang, S., Xu, C.,Song, W., Tan, S., Rong, P., Wang, W. (2016). Resveratrol inhibits Hexokinases II mediated glycolysis in non-small cell lung cancer via targeting Akt signaling pathway. Experimental cell research, 349(2), 320-327.
  • Xu, D., Jin, J., Yu, H., Zhao, Z., Ma, D., Zhang, C., Jiang, H. (2017). Chrysin inhibited tumor glycolysis and induced apoptosis in hepatocellular carcinoma by targeting hexokinase-2. Journal of Experimental & Clinical Cancer Research, 36(1), 1-11.
  • Tao, L., Wei, L., Liu, Y., Ding, Y., Liu, X., Zhang, X., Wang, X., Yao, Y., Lu, J., Wang, Q., Hu, R. (2017). Gen-27, a newly synthesized flavonoid, inhibits glycolysis and induces cell apoptosis via suppression of hexokinase II in human breast cancer cells. Biochemical pharmacology, 125, 12-25.
  • Yao, J., Liu, J., Zhao, W. (2018). By blocking hexokinase-2 phosphorylation, limonin suppresses tumor glycolysis and induces cell apoptosis in hepatocellular carcinoma. OncoTargets and therapy, 11, 3793.
Toplam 41 adet kaynakça vardır.

Ayrıntılar

Birincil Dil Türkçe
Konular Eczacılık ve İlaç Bilimleri
Bölüm Derleme
Yazarlar

Mevlüt Akdağ Bu kişi benim 0000-0002-8783-6139

Azime Berna Özçelik 0000-0002-3160-5753

Yayımlanma Tarihi 29 Ocak 2022
Gönderilme Tarihi 4 Ağustos 2021
Kabul Tarihi 24 Eylül 2021
Yayımlandığı Sayı Yıl 2022 Cilt: 46 Sayı: 1

Kaynak Göster

APA Akdağ, M., & Özçelik, A. B. (2022). GENİŞ SPEKTRUMLU ANTİKANSER BİLEŞİKLER GELİŞTİRMEYE YÖNELİK POTANSİYEL BİR HEDEF: HEKSOKİNAZ-II. Journal of Faculty of Pharmacy of Ankara University, 46(1), 182-192. https://doi.org/10.33483/jfpau.978805
AMA Akdağ M, Özçelik AB. GENİŞ SPEKTRUMLU ANTİKANSER BİLEŞİKLER GELİŞTİRMEYE YÖNELİK POTANSİYEL BİR HEDEF: HEKSOKİNAZ-II. Ankara Ecz. Fak. Derg. Ocak 2022;46(1):182-192. doi:10.33483/jfpau.978805
Chicago Akdağ, Mevlüt, ve Azime Berna Özçelik. “GENİŞ SPEKTRUMLU ANTİKANSER BİLEŞİKLER GELİŞTİRMEYE YÖNELİK POTANSİYEL BİR HEDEF: HEKSOKİNAZ-II”. Journal of Faculty of Pharmacy of Ankara University 46, sy. 1 (Ocak 2022): 182-92. https://doi.org/10.33483/jfpau.978805.
EndNote Akdağ M, Özçelik AB (01 Ocak 2022) GENİŞ SPEKTRUMLU ANTİKANSER BİLEŞİKLER GELİŞTİRMEYE YÖNELİK POTANSİYEL BİR HEDEF: HEKSOKİNAZ-II. Journal of Faculty of Pharmacy of Ankara University 46 1 182–192.
IEEE M. Akdağ ve A. B. Özçelik, “GENİŞ SPEKTRUMLU ANTİKANSER BİLEŞİKLER GELİŞTİRMEYE YÖNELİK POTANSİYEL BİR HEDEF: HEKSOKİNAZ-II”, Ankara Ecz. Fak. Derg., c. 46, sy. 1, ss. 182–192, 2022, doi: 10.33483/jfpau.978805.
ISNAD Akdağ, Mevlüt - Özçelik, Azime Berna. “GENİŞ SPEKTRUMLU ANTİKANSER BİLEŞİKLER GELİŞTİRMEYE YÖNELİK POTANSİYEL BİR HEDEF: HEKSOKİNAZ-II”. Journal of Faculty of Pharmacy of Ankara University 46/1 (Ocak 2022), 182-192. https://doi.org/10.33483/jfpau.978805.
JAMA Akdağ M, Özçelik AB. GENİŞ SPEKTRUMLU ANTİKANSER BİLEŞİKLER GELİŞTİRMEYE YÖNELİK POTANSİYEL BİR HEDEF: HEKSOKİNAZ-II. Ankara Ecz. Fak. Derg. 2022;46:182–192.
MLA Akdağ, Mevlüt ve Azime Berna Özçelik. “GENİŞ SPEKTRUMLU ANTİKANSER BİLEŞİKLER GELİŞTİRMEYE YÖNELİK POTANSİYEL BİR HEDEF: HEKSOKİNAZ-II”. Journal of Faculty of Pharmacy of Ankara University, c. 46, sy. 1, 2022, ss. 182-9, doi:10.33483/jfpau.978805.
Vancouver Akdağ M, Özçelik AB. GENİŞ SPEKTRUMLU ANTİKANSER BİLEŞİKLER GELİŞTİRMEYE YÖNELİK POTANSİYEL BİR HEDEF: HEKSOKİNAZ-II. Ankara Ecz. Fak. Derg. 2022;46(1):182-9.
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Kapsam ve Amaç

Ankara Üniversitesi Eczacılık Fakültesi Dergisi, açık erişim, hakemli bir dergi olup Türkçe veya İngilizce olarak farmasötik bilimler alanındaki önemli gelişmeleri içeren orijinal araştırmalar, derlemeler ve kısa bildiriler için uluslararası bir yayım ortamıdır. Bilimsel toplantılarda sunulan bildiriler supleman özel sayısı olarak dergide yayımlanabilir. Ayrıca, tüm farmasötik alandaki gelecek ve önceki ulusal ve uluslararası bilimsel toplantılar ile sosyal aktiviteleri içerir.