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Evaluating the Role of Nrf-2/HO-1 Pathway in Glioblastoma Treatment Efficacy: A Co-Culture Study

Year 2024, , 760 - 767, 30.09.2024

Zehra Güneş , Mehmet Furkan Başkent , Sema Arslan , Beste Atasoy , Osman Köstek , Ali Şahin , Betül Karademir Yılmaz

https://doi.org/10.33808/clinexphealthsci.1408641

Abstract

Objective: Glioblastoma (GB) is a highly lethal form of brain tumor. Although standard therapy appears to be effective, the survival time is quite short, and the recurrence rate is high. Bortezomib (BTZ), is a proteasome inhibitor, used in GB therapies and resulted in serious off-target effects. Carfilzomib (CFZ), is an alternative for BTZ, has known with nonserious off-target effects. This study aimed to examine the potential off-target effects caused by BTZ and CFZ in terms of the therapy related activation of antioxidant mechanisms regarding to Nuclear factor (erythroid-derived 2)-like 2 (Nrf-2)/Heme Oxygenase-1 (HO-1)-dependent response.
Methods: GB cells were co-cultured with heathy astrocyte (HA) cells to mimic the tumor microenvironment in some extent. Cell viability was determined following ionizing radiation (IR), temozolomide (TMZ), BTZ and CFZ alone and in combination. Nrf-2 and HO-1 protein expressions were analyzed by western blotting assay.
Results: Co-culture results showed that the GB cells in the BTZ-treated groups expressed higher levels of Nrf-2 and HO-1 than in the CFZtreated groups. In the HAs, the group treated with CFZ showed higher Nrf-2 expression than the group treated with BTZ alone, while the same groups in combination with TMZ&IR showed exactly opposite results. HO-1 expression was also not seen in any of the HA groups.
Conclusion: The significant increase in Nrf-2 levels in the CFZ-treated group in the HAs could also be interpreted as CFZ promoting the defence of healthy cells against therapy-induced stress conditions. Although further studies are needed, these preliminary results show that the evaluation of CFZ as a second-line therapy could be a milestone for the treatment of GB.

Keywords

Glioblastoma proteasome inhibitors bortezomib carfilzomib nuclear factor (erythroid-derived 2)-like 2 heme oxygenase-1

Supporting Institution

The Scientific and Technological Research Council of Turkey

Project Number

TUBITAK 118S522; TUBITAK 2209A

References

  • Razavi SM, Lee KE, Jin BE, Aujla PS, Gholamin S, Li G. Immune evasion strategies of glioblastoma. Vol. 3, Frontiers in Surgery. Frontiers Media S.A.; 2016. DOI: 10.3389/fsurg.2016.00011
  • Van Meir EG, Hadjipanayis CG, Norden AD, Shu HK, Wen PY, Olson JJ. Exciting new advances in neuro-oncology: the avenue to a cure for malignant glioma. CA: A Cancer Journal for Clinicians 2010;60(3):166–193. DOI:10.3322/caac.20069
  • Carlsson SK, Brothers SP, Wahlestedt C. Emerging treatment strategies for glioblastoma multiforme. EMBO MolecularMedicine 2014;6(11):1359–1370. DOI: 10.15252/emmm.201302627
  • Weathers SP, Gilbert MR. Current challenges in designing GBM trials for immunotherapy. Vol. 123, Journal of Neuro-Oncology. Springer New York LLC; 2015. p. 331–337. DOI:10.1007/s11060.015.1716-2
  • Stupp R, Mason WP, Van Den Bent MJ, Weller M, Fisher B, Taphoorn MJB, Belanger K, Brandes AA, Marosi C, Bogdahn U, Curschmann J, Janzer RC, Ludwin SK, Gorlia T, Allgeier A, Lacombe D, Cairncross G, Eisenhauer E, Mirimanoff RO. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. The New England Journal of Medicine 2005;352(10):987–996. DOI: DOI: 10.1056/NEJMoa043330
  • Karachi A, Dastmalchi F, Mitchell DA, Rahman M. Temozolomide for immunomodulation in the treatment of glioblastoma. Neuro-Oncology 2018;20(12):1566–1572. DOI:10.1093/neuonc/noy072
  • Sengupta S, Marrinan J, Frishman C, Sampath P. Impact of temozolomide on immune response during malignant glioma chemotherapy. Vol. 2012, Clinical and Developmental Immunology 2012. DOI:10.1155/2012/831090
  • Wang Y, Feng Y. The efficacy and safety of radiotherapy with adjuvant temozolomide for glioblastoma: A meta-analysis of randomized controlled studies. Vol. 196, Clinical Neurology and Neurosurgery Elsevier B.V.; 2020. DOI:10.1016/j.clineuro.2020.105890
  • Shahcheraghi SH, Salemi F, Alam W, Ashworth H, Saso L, Khan H, Lotfi M. The role of NRF2/KEAP1 pathway in glioblastoma: pharmacological implications. Vol. 39, Medical Oncology. Springer; 2022. DOI:10.1007/s12032.022.01693-0
  • André-Grégoire G, Bidère N, Gavard J. Temozolomide affects extracellular vesicles released by glioblastoma cells. Biochimie 2018; 155:11–15. DOI:10.1016/j.biochi.2018.02.007
  • Vlachostergios PJ, Hatzidaki E, Befani CD, Liakos P, Papandreou CN. Bortezomib overcomes MGMT-related resistance of glioblastoma cell lines to temozolomide in a scheduledependent manner. Invest New Drugs 2013;31(5):1169–1181. DOI:10.1007/s10637.013.9968-1
  • Vlachostergios PJ, Hatzidaki E, Stathakis NE, Koukoulis GK, Papandreou CN. Bortezomib downregulates MGMT expression in T98G glioblastoma cells. Cellular and Molecular Neurobiology 2013;33(3):313–318. DOI:10.1007/s10571.013.9910-2
  • Dreger H, Westphal K, Wilck N, Baumann G, Stangl V, Stangl K, Meiners S. Protection of vascular cells from oxidative stress by proteasome inhibition depends on Nrf2. Cardiovascular Research 2010;85(2):395–403. DOI:10.1093/cvr/cvp279
  • Barbagallo I, Giallongo C, Volti GL, Distefano A, Camiolo G, Raffaele M, Salerno L, Pittalà V, Sorrenti V, Avola R, Di Rosa M, Vanella L, Di Raimondo F, Tibullo D. Heme oxygenase inhibition sensitizes neuroblastoma cells to carfilzomib. Molecular Neurobiology 2019;56(2):1451–1460. DOI: 10.1007/s12035.018.1133-6
  • Mohan M, Matin A, Davies FE. Update on the optimal use of bortezomib in the treatment of multiple myeloma. Cancer Management and Research 2017; 9:51–63. DOI:10.2147/CMAR.S105163
  • Park JE, Park J, Jun Y, Oh Y, Ryoo G, Jeong YS, Gadalla HH, Min JS, Jo JH, Song MG, Kang KW, Bae SK, Yeo Y, Lee W. Expanding therapeutic utility of carfilzomib for breast cancer therapy by novel albumin-coated nanocrystal formulation. Journalof Controlled Release 2019; 302:148–159. DOI:10.1016/j.jconrel.2019.04.006
  • Jung T, Catalgol B, Grune T. The proteasomal system. Molecular Aspects of Medicine. 2009;30(4):191–296. DOI:10.1016/j.mam.2009.04.001
  • Manasanch EE, Orlowski RZ. Proteasome inhibitors in cancer therapy. Vol. 14, Nature Reviews Clinical Oncology 2017;14:417–433. DOI:10.1038/nrclinonc.2016.206
  • Kaplan GS, Torcun CC, Grune T, Ozer NK, Karademir B. Proteasome inhibitors in cancer therapy: Treatment regimen and peripheral neuropathy as a side effect. Free Radical Biology and Medicine 2017;103:1–13. DOI:10.1016/j. freeradbiomed.2016.12.007
  • Engür S, Dikmen M. Kanser Tedavisinde Proteozom İnhibitörlerinin Önemi, Erciyes Üniversitesi Fen Bilimleri Enstitüsü Dergisi 2015;31:182–190. (Turkish)
  • Karademir B, Sari G, Jannuzzi AT, Musunuri S, Wicher G, Grune T, Mi J, Hacioglu-Bay H, Forsberg-Nilsson K, Bergquist J, Jung T. Proteomic approach for understanding milder neurotoxicity of carfilzomib against bortezomib. Scientific Reports 2018;8(1). DOI:10.1038/s41598.018.34507-3
  • Vij R, Siegel DS, Jagannath S, Jakubowiak AJ, Stewart AK, Mcdonagh K, Bahlis N, Belch A, Kunkel LA, Wear S, Wong AF, Orlowski RZ, Wang M. An open-label, single-arm, phase 2 study of single-agent carfilzomib in patients with relapsed and/or refractory multiple myeloma who have been previously treated with bortezomib. British Journal of Haematology 2012;158(6):739–748. DOI:10.1111/j.1365-2141.2012.09232.x
  • Vij R, Wang M, Kaufman JL, Lonial S, Jakubowiak AJ, Stewart AK, Kukreti V, Jagannath S, McDonagh KT, Alsina M, Bahlis NJ, Reu FJ, Gabrail NY, Belch A, Matous JV, Lee P, Rosen P, Sebag M, Vesole DH, Kunkel LA, Wear SM, Wong AF, Orlowski RZ, Siegel DS. An open-label, single-arm, phase2 (PX-171-004) study of single-agent carfilzomib in bortezomibnaive patients with relapsed and/or refractory multiple myeloma. Blood 2012;119(24):5661–5670. DOI: 10.1182/blood-2012-03-414359
  • Basak P, Sadhukhan P, Sarkar P, Sil PC. Perspectives of the Nrf-2 signaling pathway in cancer progression and therapy. Toxicology Reports 2017; 4:306–318. DOI:10.1016/j.toxrep.2017.06.002
  • Awuah WA, Toufik AR, Yarlagadda R, Mikhailova T, Mehta A, Huang H, Kundu M, Lopes L, Benson S, Mykola L, Vladyslav S, Alexiou A, Alghamdi BS, Hashem AM, Ashraf GM. Exploring the role of Nrf2 signalling in glioblastoma multiforme. Discover Oncology 2022;13:94 DOI:10.1007/s12672.022.00556-4
  • Taguchi K, Yamamoto M. The KEAP1–NRF2 system as a molecular target of cancer treatment. Cancers 2021;13:1–21. DOI:10.3390/cancers13010046
  • Dikic I. Proteasomal and autophagic degradation systems. Annual Review of Biochemistry. 2017; 86:193–224. DOI:10.1146/annurev-biochem-061.516.044908
  • Zhu J, Wang H, Sun Q, Ji X, Zhu L, Cong Z, Zhou Y, Liu H, Zhou M. Nrf2 is required to maintain the self-renewal of glioma stem cells. BMC Cancer 2013;13. DOI:10.1186/1471-2407-13-380
  • Pan H, Wang H, Zhu L, Wang X, Cong Z, Sun K, Fan Y. The involvement of Nrf2-ARE pathway in regulation of apoptosis in human glioblastoma cell U251. Neurological Research 2013;35(1):71–78. DOI: 10.1179/174.313.2812Y.000.000.0094
  • Mega A, Nilsen MH, Leiss LW, Tobin NP, Miletic H, Sleire L, Strell C, Nelander S, Krona C, Hägerstrand D, Enger PØ, Nistér M, Östman A. Astrocytes enhance glioblastoma growth. Glia 2020;68(2):316–327. DOI:10.1002/glia.23718
  • Huang G, Diao J, Yi H, Xu L, Xu J, Xu W. Signaling pathways involved in HSP32 induction by hyperbaric oxygen in rat spinal neurons. Redox Biology 2016; 10:108–118. DOI:10.1016/j.redox.2016.09.011
  • Vriend J, Reiter RJ. The Keap1-Nrf2-antioxidant response element pathway: A review of its regulation by melatonin and the proteasome. Molecular and Cellular Endocrinology 2015;401:213–220. DOI:10.1016/j.mce.2014.12.013
  • Lee MH, Cha HJ, Choi EO, Han MH, Kim SO, Kim GY, Hong SH, Park C, Moon S-K, Jeong S-J, Jeong M-J, Kim W-J, ChoiYH. Antioxidant and cytoprotective effects of morin against hydrogen peroxide-induced oxidative stress are associated with the induction of Nrf-2-mediated HO-1 expression in V79-4 Chinese hamster lung fibroblasts. International Journal of Molecular Medicine 2017;39(3):672–680. DOI:10.3892/ijmm.2017.2871
  • Rushworth SA, Bowles KM, MacEwan DJ. High basal nuclear levels of Nrf2 in acute myeloid leukemia reduces sensitivity to proteasome inhibitors. Cancer Research 2011;71(5):1999–2009. DOI:10.1158/0008-5472.CAN-10-3018
  • Kitamura H, Motohashi H. NRF2 addiction in cancer cells.Cancer Science 2018; 109:900–911. DOI:10.1111/cas.13537

Year 2024, , 760 - 767, 30.09.2024

Zehra Güneş , Mehmet Furkan Başkent , Sema Arslan , Beste Atasoy , Osman Köstek , Ali Şahin , Betül Karademir Yılmaz

https://doi.org/10.33808/clinexphealthsci.1408641

Abstract

Project Number

TUBITAK 118S522; TUBITAK 2209A

References

  • Razavi SM, Lee KE, Jin BE, Aujla PS, Gholamin S, Li G. Immune evasion strategies of glioblastoma. Vol. 3, Frontiers in Surgery. Frontiers Media S.A.; 2016. DOI: 10.3389/fsurg.2016.00011
  • Van Meir EG, Hadjipanayis CG, Norden AD, Shu HK, Wen PY, Olson JJ. Exciting new advances in neuro-oncology: the avenue to a cure for malignant glioma. CA: A Cancer Journal for Clinicians 2010;60(3):166–193. DOI:10.3322/caac.20069
  • Carlsson SK, Brothers SP, Wahlestedt C. Emerging treatment strategies for glioblastoma multiforme. EMBO MolecularMedicine 2014;6(11):1359–1370. DOI: 10.15252/emmm.201302627
  • Weathers SP, Gilbert MR. Current challenges in designing GBM trials for immunotherapy. Vol. 123, Journal of Neuro-Oncology. Springer New York LLC; 2015. p. 331–337. DOI:10.1007/s11060.015.1716-2
  • Stupp R, Mason WP, Van Den Bent MJ, Weller M, Fisher B, Taphoorn MJB, Belanger K, Brandes AA, Marosi C, Bogdahn U, Curschmann J, Janzer RC, Ludwin SK, Gorlia T, Allgeier A, Lacombe D, Cairncross G, Eisenhauer E, Mirimanoff RO. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. The New England Journal of Medicine 2005;352(10):987–996. DOI: DOI: 10.1056/NEJMoa043330
  • Karachi A, Dastmalchi F, Mitchell DA, Rahman M. Temozolomide for immunomodulation in the treatment of glioblastoma. Neuro-Oncology 2018;20(12):1566–1572. DOI:10.1093/neuonc/noy072
  • Sengupta S, Marrinan J, Frishman C, Sampath P. Impact of temozolomide on immune response during malignant glioma chemotherapy. Vol. 2012, Clinical and Developmental Immunology 2012. DOI:10.1155/2012/831090
  • Wang Y, Feng Y. The efficacy and safety of radiotherapy with adjuvant temozolomide for glioblastoma: A meta-analysis of randomized controlled studies. Vol. 196, Clinical Neurology and Neurosurgery Elsevier B.V.; 2020. DOI:10.1016/j.clineuro.2020.105890
  • Shahcheraghi SH, Salemi F, Alam W, Ashworth H, Saso L, Khan H, Lotfi M. The role of NRF2/KEAP1 pathway in glioblastoma: pharmacological implications. Vol. 39, Medical Oncology. Springer; 2022. DOI:10.1007/s12032.022.01693-0
  • André-Grégoire G, Bidère N, Gavard J. Temozolomide affects extracellular vesicles released by glioblastoma cells. Biochimie 2018; 155:11–15. DOI:10.1016/j.biochi.2018.02.007
  • Vlachostergios PJ, Hatzidaki E, Befani CD, Liakos P, Papandreou CN. Bortezomib overcomes MGMT-related resistance of glioblastoma cell lines to temozolomide in a scheduledependent manner. Invest New Drugs 2013;31(5):1169–1181. DOI:10.1007/s10637.013.9968-1
  • Vlachostergios PJ, Hatzidaki E, Stathakis NE, Koukoulis GK, Papandreou CN. Bortezomib downregulates MGMT expression in T98G glioblastoma cells. Cellular and Molecular Neurobiology 2013;33(3):313–318. DOI:10.1007/s10571.013.9910-2
  • Dreger H, Westphal K, Wilck N, Baumann G, Stangl V, Stangl K, Meiners S. Protection of vascular cells from oxidative stress by proteasome inhibition depends on Nrf2. Cardiovascular Research 2010;85(2):395–403. DOI:10.1093/cvr/cvp279
  • Barbagallo I, Giallongo C, Volti GL, Distefano A, Camiolo G, Raffaele M, Salerno L, Pittalà V, Sorrenti V, Avola R, Di Rosa M, Vanella L, Di Raimondo F, Tibullo D. Heme oxygenase inhibition sensitizes neuroblastoma cells to carfilzomib. Molecular Neurobiology 2019;56(2):1451–1460. DOI: 10.1007/s12035.018.1133-6
  • Mohan M, Matin A, Davies FE. Update on the optimal use of bortezomib in the treatment of multiple myeloma. Cancer Management and Research 2017; 9:51–63. DOI:10.2147/CMAR.S105163
  • Park JE, Park J, Jun Y, Oh Y, Ryoo G, Jeong YS, Gadalla HH, Min JS, Jo JH, Song MG, Kang KW, Bae SK, Yeo Y, Lee W. Expanding therapeutic utility of carfilzomib for breast cancer therapy by novel albumin-coated nanocrystal formulation. Journalof Controlled Release 2019; 302:148–159. DOI:10.1016/j.jconrel.2019.04.006
  • Jung T, Catalgol B, Grune T. The proteasomal system. Molecular Aspects of Medicine. 2009;30(4):191–296. DOI:10.1016/j.mam.2009.04.001
  • Manasanch EE, Orlowski RZ. Proteasome inhibitors in cancer therapy. Vol. 14, Nature Reviews Clinical Oncology 2017;14:417–433. DOI:10.1038/nrclinonc.2016.206
  • Kaplan GS, Torcun CC, Grune T, Ozer NK, Karademir B. Proteasome inhibitors in cancer therapy: Treatment regimen and peripheral neuropathy as a side effect. Free Radical Biology and Medicine 2017;103:1–13. DOI:10.1016/j. freeradbiomed.2016.12.007
  • Engür S, Dikmen M. Kanser Tedavisinde Proteozom İnhibitörlerinin Önemi, Erciyes Üniversitesi Fen Bilimleri Enstitüsü Dergisi 2015;31:182–190. (Turkish)
  • Karademir B, Sari G, Jannuzzi AT, Musunuri S, Wicher G, Grune T, Mi J, Hacioglu-Bay H, Forsberg-Nilsson K, Bergquist J, Jung T. Proteomic approach for understanding milder neurotoxicity of carfilzomib against bortezomib. Scientific Reports 2018;8(1). DOI:10.1038/s41598.018.34507-3
  • Vij R, Siegel DS, Jagannath S, Jakubowiak AJ, Stewart AK, Mcdonagh K, Bahlis N, Belch A, Kunkel LA, Wear S, Wong AF, Orlowski RZ, Wang M. An open-label, single-arm, phase 2 study of single-agent carfilzomib in patients with relapsed and/or refractory multiple myeloma who have been previously treated with bortezomib. British Journal of Haematology 2012;158(6):739–748. DOI:10.1111/j.1365-2141.2012.09232.x
  • Vij R, Wang M, Kaufman JL, Lonial S, Jakubowiak AJ, Stewart AK, Kukreti V, Jagannath S, McDonagh KT, Alsina M, Bahlis NJ, Reu FJ, Gabrail NY, Belch A, Matous JV, Lee P, Rosen P, Sebag M, Vesole DH, Kunkel LA, Wear SM, Wong AF, Orlowski RZ, Siegel DS. An open-label, single-arm, phase2 (PX-171-004) study of single-agent carfilzomib in bortezomibnaive patients with relapsed and/or refractory multiple myeloma. Blood 2012;119(24):5661–5670. DOI: 10.1182/blood-2012-03-414359
  • Basak P, Sadhukhan P, Sarkar P, Sil PC. Perspectives of the Nrf-2 signaling pathway in cancer progression and therapy. Toxicology Reports 2017; 4:306–318. DOI:10.1016/j.toxrep.2017.06.002
  • Awuah WA, Toufik AR, Yarlagadda R, Mikhailova T, Mehta A, Huang H, Kundu M, Lopes L, Benson S, Mykola L, Vladyslav S, Alexiou A, Alghamdi BS, Hashem AM, Ashraf GM. Exploring the role of Nrf2 signalling in glioblastoma multiforme. Discover Oncology 2022;13:94 DOI:10.1007/s12672.022.00556-4
  • Taguchi K, Yamamoto M. The KEAP1–NRF2 system as a molecular target of cancer treatment. Cancers 2021;13:1–21. DOI:10.3390/cancers13010046
  • Dikic I. Proteasomal and autophagic degradation systems. Annual Review of Biochemistry. 2017; 86:193–224. DOI:10.1146/annurev-biochem-061.516.044908
  • Zhu J, Wang H, Sun Q, Ji X, Zhu L, Cong Z, Zhou Y, Liu H, Zhou M. Nrf2 is required to maintain the self-renewal of glioma stem cells. BMC Cancer 2013;13. DOI:10.1186/1471-2407-13-380
  • Pan H, Wang H, Zhu L, Wang X, Cong Z, Sun K, Fan Y. The involvement of Nrf2-ARE pathway in regulation of apoptosis in human glioblastoma cell U251. Neurological Research 2013;35(1):71–78. DOI: 10.1179/174.313.2812Y.000.000.0094
  • Mega A, Nilsen MH, Leiss LW, Tobin NP, Miletic H, Sleire L, Strell C, Nelander S, Krona C, Hägerstrand D, Enger PØ, Nistér M, Östman A. Astrocytes enhance glioblastoma growth. Glia 2020;68(2):316–327. DOI:10.1002/glia.23718
  • Huang G, Diao J, Yi H, Xu L, Xu J, Xu W. Signaling pathways involved in HSP32 induction by hyperbaric oxygen in rat spinal neurons. Redox Biology 2016; 10:108–118. DOI:10.1016/j.redox.2016.09.011
  • Vriend J, Reiter RJ. The Keap1-Nrf2-antioxidant response element pathway: A review of its regulation by melatonin and the proteasome. Molecular and Cellular Endocrinology 2015;401:213–220. DOI:10.1016/j.mce.2014.12.013
  • Lee MH, Cha HJ, Choi EO, Han MH, Kim SO, Kim GY, Hong SH, Park C, Moon S-K, Jeong S-J, Jeong M-J, Kim W-J, ChoiYH. Antioxidant and cytoprotective effects of morin against hydrogen peroxide-induced oxidative stress are associated with the induction of Nrf-2-mediated HO-1 expression in V79-4 Chinese hamster lung fibroblasts. International Journal of Molecular Medicine 2017;39(3):672–680. DOI:10.3892/ijmm.2017.2871
  • Rushworth SA, Bowles KM, MacEwan DJ. High basal nuclear levels of Nrf2 in acute myeloid leukemia reduces sensitivity to proteasome inhibitors. Cancer Research 2011;71(5):1999–2009. DOI:10.1158/0008-5472.CAN-10-3018
  • Kitamura H, Motohashi H. NRF2 addiction in cancer cells.Cancer Science 2018; 109:900–911. DOI:10.1111/cas.13537
There are 35 citations in total.

Details

Primary Language English
Subjects Cancer Therapy (Excl. Chemotherapy and Radiation Therapy), Molecular Targets
Journal Section Articles
Authors

Zehra Güneş 0000-0002-6090-8358

Mehmet Furkan Başkent 0000-0002-0063-8798

Sema Arslan 0000-0003-2205-0415

Beste Atasoy 0000-0003-1320-9105

Osman Köstek 0000-0002-1901-5603

Ali Şahin 0000-0001-5594-1551

Betül Karademir Yılmaz 0000-0003-1762-0284

Project Number TUBITAK 118S522; TUBITAK 2209A
Early Pub Date September 27, 2024
Publication Date September 30, 2024
Submission Date December 22, 2023
Acceptance Date June 22, 2024
Published in Issue Year 2024

Cite

APA Güneş, Z., Başkent, M. F., Arslan, S., Atasoy, B., et al. (2024). Evaluating the Role of Nrf-2/HO-1 Pathway in Glioblastoma Treatment Efficacy: A Co-Culture Study. Clinical and Experimental Health Sciences, 14(3), 760-767. https://doi.org/10.33808/clinexphealthsci.1408641
AMA Güneş Z, Başkent MF, Arslan S, Atasoy B, Köstek O, Şahin A, Karademir Yılmaz B. Evaluating the Role of Nrf-2/HO-1 Pathway in Glioblastoma Treatment Efficacy: A Co-Culture Study. Clinical and Experimental Health Sciences. September 2024;14(3):760-767. doi:10.33808/clinexphealthsci.1408641
Chicago Güneş, Zehra, Mehmet Furkan Başkent, Sema Arslan, Beste Atasoy, Osman Köstek, Ali Şahin, and Betül Karademir Yılmaz. “Evaluating the Role of Nrf-2/HO-1 Pathway in Glioblastoma Treatment Efficacy: A Co-Culture Study”. Clinical and Experimental Health Sciences 14, no. 3 (September 2024): 760-67. https://doi.org/10.33808/clinexphealthsci.1408641.
EndNote Güneş Z, Başkent MF, Arslan S, Atasoy B, Köstek O, Şahin A, Karademir Yılmaz B (September 1, 2024) Evaluating the Role of Nrf-2/HO-1 Pathway in Glioblastoma Treatment Efficacy: A Co-Culture Study. Clinical and Experimental Health Sciences 14 3 760–767.
IEEE Z. Güneş, M. F. Başkent, S. Arslan, B. Atasoy, O. Köstek, A. Şahin, and B. Karademir Yılmaz, “Evaluating the Role of Nrf-2/HO-1 Pathway in Glioblastoma Treatment Efficacy: A Co-Culture Study”, Clinical and Experimental Health Sciences, vol. 14, no. 3, pp. 760–767, 2024, doi: 10.33808/clinexphealthsci.1408641.
ISNAD Güneş, Zehra et al. “Evaluating the Role of Nrf-2/HO-1 Pathway in Glioblastoma Treatment Efficacy: A Co-Culture Study”. Clinical and Experimental Health Sciences 14/3 (September 2024), 760-767. https://doi.org/10.33808/clinexphealthsci.1408641.
JAMA Güneş Z, Başkent MF, Arslan S, Atasoy B, Köstek O, Şahin A, Karademir Yılmaz B. Evaluating the Role of Nrf-2/HO-1 Pathway in Glioblastoma Treatment Efficacy: A Co-Culture Study. Clinical and Experimental Health Sciences. 2024;14:760–767.
MLA Güneş, Zehra et al. “Evaluating the Role of Nrf-2/HO-1 Pathway in Glioblastoma Treatment Efficacy: A Co-Culture Study”. Clinical and Experimental Health Sciences, vol. 14, no. 3, 2024, pp. 760-7, doi:10.33808/clinexphealthsci.1408641.
Vancouver Güneş Z, Başkent MF, Arslan S, Atasoy B, Köstek O, Şahin A, Karademir Yılmaz B. Evaluating the Role of Nrf-2/HO-1 Pathway in Glioblastoma Treatment Efficacy: A Co-Culture Study. Clinical and Experimental Health Sciences. 2024;14(3):760-7.

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