Tinjauan Literatur: Efektivitas Butionin Sulfoksimin Dalam Meningkatkan Sensitivitas Sel Kanker Terhadap Agen Kemoterapi Secara In Vivo

Khoerunnisa Azamy(1), Wahyu Utami(2*)

(1) Fakultas Farmasi Universitas Muhammadiyah Surakarta
(2) Faculty of Pharmacy Universitas Muhammadiyah Surakarta
(*) Corresponding Author

Abstract

Glutathione (GSH) is one of the targets to overcome chemotherapy resistance. Cancer cells adapt by increasing the production of GSH which acts as an antioxidant to reduce the reactive oxygen species (ROS)-inducing of chemotherapy agents. GSH can bind to chemotherapy agents that are electrophile resulting a conjugate of electrophile-GSH which is more polar so it is easily excreted out of the body. Butionine sulfoximine (BS) is a GSH inhibitor that decrease the concentration of GSH in cells. BS is a γ-glutamyl- cysteine ligase (GCL) enzyme inhibitor that catalyzes the first steps of GSH synthesis. This literature review aims to evaluate the use of BS to sensitize cancer cells against chemotherapy in vivo. The literature search was carried out of two databases (Pubmed and Sciendirect) resulting in 357 journals. Furthermore, a selection process was carried out which yielded in 10 journals. BS synergize with chemotherapy of alkylating groups, vincristine, geftinib, and cytarabine+doxorubicin and significantly increases the effectiveness of therapy compared to chemotherapy only. However, BS delay cancer in initiation phase, and not in tumor progression phase. In vivo, the combination of BS and chemotherapy of alkylating groups, vincristine, geftinib, and cytarabine+doxorubicin reduce the tumor volume, cancer cell proliferation and also increasing the survival of experimental animals.

Keywords

cancer; glutathione; buthionine sulfoximine; in vivo

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References

Albano, R., Raddatz, N. J., Hjelmhaug, J., Baker, D. A., & Lobner, D., 2015, Regulation of system xc- by pharmacological manipulation of cellular thiols, Oxidative Medicine and Cellular Longevity, 2015.

Bansal, A., & Celeste Simon, M., 2018, Glutathione metabolism in cancer progression and treatment resistance, Journal of Cell Biology, 217(7), 2291–2298.

Brentnall, M., Rodriguez-Menocal, L., De Guevara, R. L., Cepero, E., & Boise, L. H., 2013, Caspase-9, caspase-3 and caspase-7 have distinct roles during intrinsic apoptosis. BMC cell biology, 14, 32.

Burkhart, C. A., Watt, F., Murray, J., Pajic, M., Prokvolit, A., Xue, C., Flemming, C., Smith, J., Purmal, A., Isachenko, N., Komarov, P. G., Gurova, K. V., Sartorelli, A. C., Marshall, G. M., Norris, M. D., Gudkov, A. V., & Haber, M., 2009, Small-molecule multidrug resistance-associated protein 1 inhibitor reversan increases the therapeutic index of chemotherapyin mouse models of neuroblastoma, Cancer Research, 69(16), 6573–6580.

Carter, D. R., Sutton, S. K., Pajic, M., Murray, J., Sekyere, E. O., Fletcher, J., Beckers, A., De Preter, K., Speleman, F., George, R. E., Haber, M., Norris, M. D., Cheung, B. B., & Marshall, G. M., 2016, Glutathione biosynthesis is upregulated at the initiation of MYCN-driven neuroblastoma tumorigenesis, Molecular Oncology, 10(6), 866–878.

Chen, H., Zhou, L., Lin, C. Y., Beattie, M. C., Liu, J., & Zirkin, B. R., 2010, Effect of glutathione redox state on Leydig cell susceptibility to acute oxidative stress, Molecular and Cellular Endocrinology, 323(2), 147–154.

Chio, I. I. C., & Tuveson, D. A., 2017, ROS in Cancer: The Burning Question, Trends in Molecular Medicine (Vol. 23, Issue 5, pp. 411–429). Elsevier Ltd.

Cole, S. P. C., & Deeley, R. G., 2006, Transport of glutathione and glutathione conjugates by MRP1, Trends in Pharmacological Sciences (Vol. 27, Issue 8, pp. 438–446). Elsevier.

Cooper, A. J. L., & Hanigan, M. H., 2018, Metabolism of Glutathione S-Conjugates: Multiple Pathways, Comprehensive Toxicology: Third Edition (Vols. 10–15, pp. 363– 406). Elsevier Inc.

Deeley, R. G., Westlake, C., & Cole, S. P. C., 2006, Transmembrane Transport of Endo- and Xenobiotics by Mammalian ATP-Binding Cassette Multidrug Resistance Proteins, Physiological Reviews, 86(3), 849–899.

Desideri, E., Ciccarone, F., & Ciriolo, M. R., 2019, Targeting glutathione metabolism: Partner in crime in anticancer therapy, Nutrients (Vol. 11, Issue 8). MDPI AG.

Espinosa-Diez, C., Miguel, V., Mennerich, D., Kietzmann, T., Sánchez-Pérez, P., Cadenas, S., & Lamas, S., 2015, Antioxidant responses and cellular adjustments to oxidative stress, Redox biology, 6, 183–197.

Forman, H. J., Zhang, H., & Rinna, A., 2009, Glutathione: Overview of its protective roles, measurement, and biosynthesis, Molecular Aspects of Medicine (Vol. 30, Issues 1–2, pp. 1–12). NIH Public Access.

Forte, D., García-Fernández, M., Sánchez-Aguilera, A., Stavropoulou, V., Fielding, C., Martín-Pérez, D., López, J. A., Costa, A. S. H., Tronci, L., Nikitopoulou, E., Barber, M., Gallipoli, P., Marando, L., Fernández de Castillejo, C. L., Tzankov, A., Dietmann, S., Cavo, M., Catani, L., Curti, A., … Méndez-Ferrer, S., 2020, Bone Marrow Mesenchymal Stem Cells Support Acute Myeloid Leukemia Bioenergetics and Enhance Antioxidant Defense and Escape from Chemotherapy, Cell Metabolism.

Franco, R., Bortner, C. D., Schmitz, I., & Cidlowski, J. A., 2014, Glutathione depletion regulates both extrinsic and intrinsic apoptotic signaling cascades independent from multidrug resistance protein 1, Apoptosis, 19(1), 117–134.

Gross, M. I., Demo, S. D., Dennison, J. B., Chen, L., Chernov-Rogan, T., Goyal, B., Janes, J. R., Laidig, G. J., Lewis, E. R., Li, J., Mackinnon, A. L., Parlati, F., Rodriguez, M. L., Shwonek, P. J., Sjogren, E. B., Stanton, T. F., Wang, T., Yang, J., Zhao, F., & Bennett, M. K., 2014, Antitumor activity of the glutaminase inhibitor CB-839 in triple-negative breast cancer, Molecular cancer therapeutics, 13(4), 890–901.

Habtetsion, T., Ding, Z. C., Pi, W., Li, T., Lu, C., Chen, T., Xi, C., Spartz, H., Liu, K., Hao, Z., Mivechi, N., Huo, Y., Blazar, B. R., Munn, D. H., & Zhou, G., 2018, Alteration of Tumor Metabolism by CD4+ T Cells Leads to TNF-α-Dependent Intensification of Oxidative Stress and Tumor Cell Death, Cell Metabolism, 28(2), 228-242.e6.

Harris, I. S., Treloar, A. E., Inoue, S., Sasaki, M., Gorrini, C., Lee, K. C., Yung, K. Y., Brenner, D., Knobbe-Thomsen, C. B., Cox, M. A., Elia, A., Berger, T., Cescon, D. W., Adeoye, A., Brüstle, A., Molyneux, S. D., Mason, J. M., Li, W. Y., Yamamoto, K., … Mak, T. W., 2015, Glutathione and Thioredoxin Antioxidant Pathways Synergize to Drive Cancer Initiation and Progression, Cancer Cell, 27(2), 211–222.

Huang, Z.-Z., Chen, C., Zeng, Z., Yang, H., Oh, J., Chen, L., & C. Lu, S., 2001, Mechanism and significance of increased glutathione level in human hepatocellular carcinoma and liver regeneration, The FASEB Journal, 15(1), 19–21.

Huang, Y., Dai, Z., Barbacioru, C., & Sadée, W., 2005, Cystine-Glutamate Transporter SLC7A11 in Cancer Chemosensitivity and Chemoresistance, Cancer Research, 65(16), 7446 LP – 7454.

Huo, H., Zhou, Z., Qin, J., Liu, W., Wang, B., & Gu, Y., 2016, Erastin disrupts mitochondrial permeability transition pore (mPTP) and induces apoptotic death of colorectal cancer cells, PLoS ONE, 11(5).

Issa, F., Ioppolo, J. A., & Rendina, L. M., 2013, 3.30 - Boron and Gadolinium Neutron Capture Therapy (J. Reedijk & K. B. T.-C. I. C. I. I. (Second E. Poeppelmeier (eds.); pp. 877–900). Elsevier.

Jaramillo, M. C., & Zhang, D. D., 2013, The emerging role of the Nrf2-Keap1 signaling pathway in cancer, Genes and Development (Vol. 27, Issue 20, pp. 2179–2191). Cold Spring Harbor Laboratory Press.

Jia, Y., Wang, H. D., Wang, Q., Ding, H., Wu, H. M., & Pan, H., 2017, GSH depletion and consequent AKT inhibition contribute to the Nrf2 knockdown-induced decrease in proliferation in glioblastoma U251 cells, Oncology Reports, 37(4), 2252–2260.

Kim, S. J., Kim, H. S., & Seo, Y. R., 2019, Understanding of ROS-Inducing Strategy in Anticancer Therapy, Oxidative Medicine and Cellular Longevity (Vol. 2019). Hindawi Limited.

Kotamraju, S., Chitambar, C. R., Kalivendi, S. V., Joseph, J., & Kalyanaraman, B., 2002). Transferrin receptor-dependent iron uptake is responsible for doxorubicin-mediated apoptosis in endothelial cells. Role of oxidant-induced iron signaling in apoptosis, Journal of Biological Chemistry, 277(19), 17179–17187.

Lan, D., Wang, L., He, R., Ma, J., Bin, Y., Chi, X., Chen, G., & Cai, Z., 2018, Exogenous glutathione contributes to cisplatin resistance in lung cancer A549 cells, American Journal of Translational Research, 10(5), 1295–1309.

Li, Y., Yan, H., Xu, X., Liu, H., Wu, C., & Zhao, L., 2020, Erastin/sorafenib induces cisplatin-resistant non-small cell lung cancer cell ferroptosis through inhibition of the Nrf2/xCT pathway, Oncology Letters, 19(1), 323–333.

Lien, E. C., Lyssiotis, C. A., Juvekar, A., Hu, H., Asara, J. M., Cantley, L. C., & Toker, A., 2016, Glutathione biosynthesis is a metabolic vulnerability in PI(3)K/Akt-driven breast cancer, Nature Cell Biology, 18(5), 572–578.

Loe, D. W., Almquist, K. C., Deeley, R. G., & Cole, S. P. C., 1996, Multidrug resistance protein (MRP)-mediated transport of leukotriene C4 and chemotherapeutic agents in membrane vesicles: Demonstration of glutathione-dependent vincristine transport, Journal of Biological Chemistry, 271(16), 9675–9682.

Ma, Q., 2013, Role of Nrf2 in Oxidative Stress and Toxicity, Annual Review of Pharmacology and Toxicology, 53(1), 401–426.

Manohar, C. F., Bray, J. A., Salwen, H. R., Madafiglio, J., Cheng, A., Flemming, C., Marshall, G. M., Norris, M. D., Haber, M., & Cohn, S. L., 2004, MYCN-mediated regulation of the MRP1 promoter in human neuroblastoma, Oncogene, 23(3), 753–762.

Marchan, R., Hammond, C. L., & Ballatori, N., 2008, Multidrug resistance-associated protein 1 as a major mediator of basal and apoptotic glutathione release, Biochimica et Biophysica Acta - Biomembranes, 1778(10), 2413–2420.

Markovic, J., Mora, N. J., Broseta, A. M., Gimeno, A., de-la-Concepción, N., Viña, J., & Pallardó, F. V., 2009, The Depletion of Nuclear Glutathione Impairs Cell Proliferation in 3t3 Fibroblasts, PLoS ONE, 4(7), e6413.

Marullo, R., Werner, E., Degtyareva, N., Moore, B., Altavilla, G., Ramalingam, S. S., & Doetsch, P. W., 2013, Cisplatin Induces a Mitochondrial-ROS Response That Contributes to Cytotoxicity Depending on Mitochondrial Redox Status and Bioenergetic Functions, PLoS ONE, 8(11), e81162.

McBrayer, S. K., Mayers, J. R., DiNatale, G. J., Shi, D. D., Khanal, J., Chakraborty, A. A., Sarosiek, K. A., Briggs, K. J., Robbins, A. K., Sewastianik, T., Shareef, S. J., Olenchock, B. A., Parker, S. J., Tateishi, K., Spinelli, J. B., Islam, M., Haigis, M. C., Looper, R. E., Ligon, K. L., … Kaelin, W. G., 2018, Transaminase Inhibition by 2- Hydroxyglutarate Impairs Glutamate Biosynthesis and Redox Homeostasis in Glioma, Cell, 175(1), 101--116.e25.

Meister, A., & Anderson, M. E., 1983, Glutathione, Annual Review of Biochemistry, 52(1), 711–760.

Mirkovic, N., Voehringer, D. W., Story, M. D., McConkey, D. J., McDonnell, T. J., & Meyn, R. E., 1997, Resistance to radiation-induced apoptosis in Bcl-2-expressing cells is reversed by depleting cellular thiols, Oncogene, 15(12), 1461–1470.

Okon, I. S., Coughlan, K. A., Zhang, M., Wang, Q., & Zou, M. H., 2015, Gefitinib-mediated reactive oxygen specie (ROS) instigates mitochondrial dysfunction and drug resistance in lung cancer cells, Journal of Biological Chemistry, 290(14), 9101–9110.

Okuno, S., Sato, H., Kuriyama-Matsumura, K., Tamba, M., Wang, H., Sohda, S., Hamada, H., Yoshikawa, H., Kondo, T., & Bannai, S., 2003, Role of cystine transport in intracellular glutathione level and cisplatin resistance in human ovarian cancer cell lines, British journal of cancer, 88(6), 951–956.

Piskounova, E., Agathocleous, M., Murphy, M. M., Hu, Z., Huddlestun, S. E., Zhao, Z., Leitch, A. M., Johnson, T. M., DeBerardinis, R. J., & Morrison, S. J., 2015, Oxidative stress inhibits distant metastasis by human melanoma cells, Nature, 527(7577), 186–191.

Pizzorno, J., 2014, Glutathione! Integrative Medicine (Encinitas, Calif.), 13(1), 8–12.

Raza, A., Galili, N., Mulford, D., Smith, S. E., Brown, G. L., Steensma, D. P., Lyons, R. M., Boccia, R., Sekeres, M. A., Garcia-Manero, G., & Mesa, R. A., 2012, Phase 1 dose- ranging study of ezatiostat hydrochloride in combination with lenalidomide in patients with non-deletion (5q) low to intermediate-1 risk myelodysplastic syndrome (MDS), Journal of hematology & oncology, 5, 18.

Robe, P. A., Martin, D. H., Nguyen-Khac, M. T., Artesi, M., Deprez, M., Albert, A., Vanbelle, S., Califice, S., Bredel, M., & Bours, V., 2009, Early termination of ISRCTN45828668, a phase 1/2 prospective, randomized study of sulfasalazine for the treatment of progressing malignant gliomas in adults, BMC Cancer, 9, 372.

Rocha, C R R, Garcia, C. C. M., Vieira, D. B., Quinet, A., de Andrade-Lima, L. C., Munford, V., Belizário, J. E., & Menck, C. F. M., 2014, Glutathione depletion sensitizes cisplatin- and temozolomide-resistant glioma cells in vitro and in vivo, Cell Death & Disease, 5(10), e1505–e1505.

Rocha, Clarissa Ribeiro Reily, Kajitani, G. S., Quinet, A., Fortunato, R. S., & Menck, C. F. M., 2016, NRF2 and glutathione are key resistance mediators to temozolomide in glioma and melanoma cells, Oncotarget, 7(30), 48081–48092.

Rocha, G. da G., Oliveira, R. R., Kaplan, M. A. C., & Gattass, C. R., 2014, 3β-Acetyl tormentic acid reverts MRP1/ABCC1 mediated cancer resistance through modulation of intracellular levels of GSH and inhibition of GST activity, European Journal of Pharmacology, 741, 140–149.

Sato, M., Kusumi, R., Hamashima, S., Kobayashi, S., Sasaki, S., Komiyama, Y., Izumikawa, T., Conrad, M., Bannai, S., & Sato, H., 2018, The ferroptosis inducer erastin irreversibly inhibits system xc- and synergizes with cisplatin to increase cisplatin’s cytotoxicity in cancer cells, Scientific Reports, 8(1).

Sau, A., Pellizzari Tregno, F., Valentino, F., Federici, G., & Caccuri, A. M., 2010, Glutathione transferases and development of new principles to overcome drug resistance, Archives of Biochemistry and Biophysics, 500(2), 116–122.

Selwan, E. M., & Edinger, A. L., 2017, Branched chain amino acid metabolism and cancer: the importance of keeping things in context, Translational Cancer Research, 6(3).

Shi, X., Wang, J., Lei, Y., Cong, C., Tan, D., & Zhou, X., 2019, Research progress on the PI3K/AKT signaling pathway in gynecological cancer (Review), Molecular Medicine Reports, 19(6), 4529–4535.

Suh, E. H., Hackett, E. P., Wynn, R. M., Chuang, D. T., Zhang, B., Luo, W., Sherry, A. D., & Park, J. M., 2019, In vivo assessment of increased oxidation of branched-chain amino acids in glioblastoma, Scientific Reports, 9(1), 1–9.

Tagde, A., Singh, H., Kang, M. H., & Reynolds, C. P., 2014, The glutathione synthesis inhibitor buthionine sulfoximine synergistically enhanced melphalan activity against preclinical models of multiple myeloma, Blood Cancer Journal, 4(7).

Tang, B., Zhu, J., Li, J., Fan, K., Gao, Y., Cheng, S., Kong, C., Zheng, L., Wu, F., Weng, Q., Lu, C., & Ji, J., 2020, The ferroptosis and iron-metabolism signature robustly predicts clinical diagnosis, prognosis and immune microenvironment for hepatocellular carcinoma, Cell Communication and Signaling, 18(1).

Tian, T., Wang, M., & Ma, D., 2014, TNF-α, a good or bad factor in hematological diseases?, Stem cell investigation, 1, 12.

Traverso, N., Ricciarelli, R., Nitti, M., Marengo, B., Furfaro, A. L., Pronzato, M. A., Marinari, U. M., & Domenicotti, C., 2013, Role of glutathione in cancer progression and chemoresistance, Oxidative Medicine and Cellular Longevity.

van Gastel, N., Spinelli, J. B., Sharda, A., Schajnovitz, A., Baryawno, N., Rhee, C., Oki, T., Grace, E., Soled, H. J., Milosevic, J., Sykes, D. B., Hsu, P. P., Vander Heiden, M. G., Vidoudez, C., Trauger, S. A., Haigis, M. C., & Scadden, D. T., 2020, Induction of a Timed Metabolic Collapse to Overcome Cancer Chemoresistance, Cell Metabolism, 32(3), 391-403.e6.

Villablanca, J. G., Volchenboum, S. L., Cho, H., Kang, M. H., Cohn, S. L., Anderson, C. P., Marachelian, A., Groshen, S., Tsao-Wei, D., Matthay, K. K., Maris, J. M., Hasenauer, C. E., Czarnecki, S., Lai, H., Goodarzian, F., Shimada, H., & Reynolds, C. P., 2016, A Phase I New Approaches to Neuroblastoma Therapy Study of Buthionine Sulfoximine and Melphalan With Autologous Stem Cells for Recurrent/Refractory High-Risk Neuroblastoma, Pediatric Blood and Cancer, 63(8), 1349–1356.

Wang, Yijun, Lu, H., Wang, D., Li, S., Sun, K., Wan, X., Taylor, E. W., & Zhang, J., 2012, Inhibition of glutathione synthesis eliminates the adaptive response of ascitic hepatoma 22 cells to nedaplatin that targets thioredoxin reductase, Toxicology and Applied Pharmacology, 265(3), 342–350.

Wang, Yuetong, Zhang, J., Ren, S., Sun, D., Huang, H. Y., Wang, H., Jin, Y., Li, F., Zheng, C., Yang, L., Deng, L., Jiang, Z., Jiang, T., Han, X., Hou, S., Guo, C., Li, F., Gao, D., Qin, J., … Ji, H., 2019, Branched-Chain Amino Acid Metabolic Reprogramming Orchestrates Drug Resistance to EGFR Tyrosine Kinase Inhibitors, Cell Reports, 28(2), 512----525.e6.

Zhang, P., Wang, W., Wei, Z., Xu, L. I., Yang, X., & DU, Y., 2016., xCT expression modulates cisplatin resistance in Tca8113 tongue carcinoma cells, Oncology letters, 12(1), 307–314.

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