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Cytotoxic and antioxidant effects of paclitaxel and glutathione combination on breast cancer cell line

Yıl 2024, Cilt: 10 Sayı: 3, 200 - 210, 31.12.2024
https://doi.org/10.30569/adiyamansaglik.1525999

Öz

Aim: The aim of this study was to investigate the effects of glutathione (GSH) on chemotherapy-related toxicities in MCF-7 breast cancer cell line treated with paclitaxel (PTX) by cell viability and oxsidative stres parameters.
Materials and Methods: Cells were treated with glutathione (2.5-20 mM) and paclitaxel (0.001-100 µM) for 24, 48 and 72 hours, after which cell viability was determined by WST-1 assay. IC50 values were calculated from the data obtained. Following combination analyses, the combination index was calculated and the levels of glutathione, total oxidant species (TOS) and total antioxidant species (TAS) were measured in cell lysates exposed to the indicated combinations for 72 hours.
Results: In the study, it was determined that the cytotoxic effect of paclitaxel decreased as the amount of glutathion used in the combinations increased and glutathion concentrations above 10 mM showed antagonistic effect with paclitaxel.
Conclusion: In patients with breast cancer, the administration of appropriate doses of glutathione in combination with chemotherapy may prove beneficial in reducing the adverse effects associated with oxidative stress.

Etik Beyan

Ethical approval was not required as this study did not involve animal or human experimentation.

Destekleyen Kurum

This study was supported by Adnan Menderes University Scientific Research Projects Unit with the project coded VTF-15054.

Proje Numarası

the project coded VTF-15054

Kaynakça

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  • Siegel RL, Miller KD, Wagle NS, Jemal A. Cancer statistics, 2023. CA Cancer J Clin. 2023;73(1):17-48. doi:10.3322/caac.21763.
  • Burguin A, Diorio C, Durocher F. Breast Cancer Treatments: Updates and New Challenges. J Pers Med. 2021;11(8):808. doi:10.3390/jpm11080808.
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  • Ashrafizadeh M, Zarrabi A, Hashemi F, et al. Curcumin in cancer therapy: A novel adjunct for combination chemotherapy with paclitaxel and alleviation of its adverse effects. Life Sci. 2020;256:117984. doi:10.1016/j.lfs.2020.117984
  • Zhao, S., Tang, Y., Wang, R. et al. Mechanisms of cancer cell death induction by paclitaxel: an updated review. Apoptosis. 2022; 27: 647-667. doi:10.1007/s10495-022-01750-z
  • Behranvand N, Nasri F, Zolfaghari Emameh R, et al. Chemotherapy: a double-edged sword in cancer treatment. Cancer Immunol Immunother. 2022;71(3):507-526. doi:10.1007/s00262-021-03013-3
  • van den Boogaard WMC, Komninos DSJ, Vermeij WP. Chemotherapy side-effects: not all dna damage ıs equal. Cancers (Basel). 2022;14(3):627. doi:10.3390/cancers14030627.
  • Mansoori B, Mohammadi A, Davudian S, Shirjang S, Baradaran B. The different mechanisms of cancer drug resistance: a brief review. Adv Pharm Bull. 2017;7(3):339-348. doi:10.15171/apb.2017.041.
  • Anand U, Dey A, Chandel AKS, et al. Cancer chemotherapy and beyond: Current status, drug candidates, associated risks and progress in targeted therapeutics. Genes Dis. 2022;10(4):1367-1401. doi:10.1016/j.gendis.2022.02.007
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Paklitaksel ile glutatyon kombinasyonunun meme kanseri hücre hattında sitotoksik ve antioksidan etkileri

Yıl 2024, Cilt: 10 Sayı: 3, 200 - 210, 31.12.2024
https://doi.org/10.30569/adiyamansaglik.1525999

Öz

Amaç: Bu çalışmanın amacı Paklitaksel (PTX) ile tedavi edilen MCF-7 meme kanseri hücre hattında glutatyonun (GSH) kemoterapi ile ilişkili toksisiteler üzerindeki etkilerini hücre canlılığı ve oksidatif stres parametreleri ile araştırmaktır.
Gereç ve Yöntem: Hücreler 24, 48 ve 72 saat boyunca glutatyon (2,5-20 mM) ve paklitaksel (0,001-100 µM) ile muamele edilmiş, ardından hücre canlılığı WST-1 testi ile belirlenmiştir. Elde edilen verilerden IC50 değerleri hesaplanmıştır. Kombinasyon analizlerinin ardından kombinasyon indeksi hesaplanmış ve 72 saat boyunca belirtilen kombinasyonlara maruz bırakılan hücre lizatlarında glutatyon, toplam oksidan türler (TOS) ve toplam antioksidan türler (TAS) seviyeleri ölçülmüştür.
Bulgular: Çalışmada, kombinasyonlarda kullanılan glutatyon miktarı arttıkça paklitakselin sitotoksik etkisinin azaldığı ve 10 mM üzerindeki glutatyon konsantrasyonlarının paklitaksel ile antagonistik etki gösterdiği tespit edilmiştir.
Sonuç: Meme kanseri hastalarında, kemoterapi ile birlikte uygun dozlarda glutatyon uygulanması, oksidatif stres ile ilişkili olumsuz etkileri azaltmada faydalı olabilir.

Etik Beyan

Ethical approval was not required as this study did not involve animal or human experimentation.

Destekleyen Kurum

This study was supported by Adnan Menderes University Scientific Research Projects Unit with the project coded VTF-15054.

Proje Numarası

the project coded VTF-15054

Kaynakça

  • Feng Y, Spezia M, Huang S, et al. Breast cancer development and progression: Risk factors, cancer stem cells, signaling pathways, genomics, and molecular pathogenesis. Genes & Diseases.2018;5(2):77-106. doi:10.1016/j.gendis.2018.05.001.
  • Siegel RL, Miller KD, Wagle NS, Jemal A. Cancer statistics, 2023. CA Cancer J Clin. 2023;73(1):17-48. doi:10.3322/caac.21763.
  • Burguin A, Diorio C, Durocher F. Breast Cancer Treatments: Updates and New Challenges. J Pers Med. 2021;11(8):808. doi:10.3390/jpm11080808.
  • Longchar A, Prasad SB. Biochemical changes associated with ascorbic acid-cisplatin combination therapeutic efficacy and protective effect on cisplatin-induced toxicity in tumor-bearing mice. Toxicol Rep. 2015;2:489-503. doi:10.1016/j.toxrep.2015.01.017.
  • Ashrafizadeh M, Zarrabi A, Hashemi F, et al. Curcumin in cancer therapy: A novel adjunct for combination chemotherapy with paclitaxel and alleviation of its adverse effects. Life Sci. 2020;256:117984. doi:10.1016/j.lfs.2020.117984
  • Zhao, S., Tang, Y., Wang, R. et al. Mechanisms of cancer cell death induction by paclitaxel: an updated review. Apoptosis. 2022; 27: 647-667. doi:10.1007/s10495-022-01750-z
  • Behranvand N, Nasri F, Zolfaghari Emameh R, et al. Chemotherapy: a double-edged sword in cancer treatment. Cancer Immunol Immunother. 2022;71(3):507-526. doi:10.1007/s00262-021-03013-3
  • van den Boogaard WMC, Komninos DSJ, Vermeij WP. Chemotherapy side-effects: not all dna damage ıs equal. Cancers (Basel). 2022;14(3):627. doi:10.3390/cancers14030627.
  • Mansoori B, Mohammadi A, Davudian S, Shirjang S, Baradaran B. The different mechanisms of cancer drug resistance: a brief review. Adv Pharm Bull. 2017;7(3):339-348. doi:10.15171/apb.2017.041.
  • Anand U, Dey A, Chandel AKS, et al. Cancer chemotherapy and beyond: Current status, drug candidates, associated risks and progress in targeted therapeutics. Genes Dis. 2022;10(4):1367-1401. doi:10.1016/j.gendis.2022.02.007
  • Debela DT, Muzazu SG, Heraro KD, et al. New approaches and procedures for cancer treatment: Current perspectives. SAGE Open Med. 2021;9:20503121211034366. doi:10.1177/20503121211034366
  • Valenti G, Tasso B, Traverso N, Domenicotti C, Marengo B. Glutathione in cancer progression and chemoresistance: an update. REM. 2023; (1), e220023. doi: 10.1530/REM-22-0023.
  • Block KI, Koch AC, Mead MN, Tothy PK, Newman RA, Gyllenhaal C. Impact of antioxidant supplementation on chemotherapeutic toxicity: a systematic review of the evidence from randomized controlled trials. Int J Cancer. 2008;15;123(6):1227-1239. doi: 10.1002/ijc.23754. PMID: 18623084.
  • Vatankhah MA, Panahizadeh R, Nejati-Koshki K, Arabzadeh M, Arabzadeh AA, Najafzadeh N. Curcumin Upregulates miR-148a to increase the chemosensitivity of CD44-Positive prostate Cancer stem cells to Paclitaxel through targeting the MSK1/IRS1 axis. Drug Res. 2022;72(08):457-465.
  • Estrela JM, Ortega A, Obrador E. Glutathione in cancer biology and therapy. Crit Rev Clin Lab Sci. 2006;43(2):143-81. doi: 10.1080/10408360500523878. PMID: 16517421.
  • Aquilano K, Baldelli S, Ciriolo MR. Glutathione: new roles in redox signaling for an old antioxidant. Front Pharmacol. 2014;5:196. doi:10.3389/fphar.2014.00196
  • Balendiran GK, Dabur R, Fraser D. The role of glutathione in cancer. Cell Biochem Funct. 2004;22(6):343-352. doi:10.1002/cbf.1149
  • Pastore A, Federici G, Bertini E, Piemonte F. Analysis of glutathione: implication in redox and detoxification. Clin Chim Acta. 2003;333(1):19-39. doi:10.1016/s0009-8981(03)00200-6.
  • Zhang H, Forman HJ. Glutathione synthesis and its role in redox signaling. Semin Cell Dev Biol. 2012;23(7):722-728. doi:10.1016/j.semcdb.2012.03.017
  • Teixeira FK, Menezes-Benavente L, Galvão VC, Margis-Pinheiro M. Multigene families encode the major enzymes of antioxidant metabolism in Eucalyptus grandis L. Genet Mol Biol. 2005;28(3):529-538. doi:10.1590/S1415-47572005000400007.
  • Sandhya T, Mishra KP. Cytotoxic response of breast cancer cell lines, MCF 7 and T 47 D to triphala and its modification by antioxidants. Cancer Lett. 2006;238(2):304-313. doi:10.1016/j.canlet.2005.07.013.
  • Shakhristova EV, Stepovaya EA, Ryazantseva NV, et al. Role of glutathione system redox potential in apoptosis dysregulation in MCF-7 breast adenocarcinoma. Bull Exp Biol Med. 2016;160(3):364-367. doi:10.1007/s10517-016-3172-1.
  • Theodossiou TA, Olsen CE, Jonsson M, Kubin A, Hothersall JS, Berg K. The diverse roles of glutathione-associated cell resistance against hypericin photodynamic therapy. Redox Biol. 2017;12:191-197. doi:10.1016/j.redox.2017.02.018.
  • Kennedy L, Sandhu JK, Harper ME, Cuperlovic-Culf M. Role of glutathione in cancer: from mechanisms to therapies. Biomolecules. 2020;10(10):1429. doi:10.3390/biom10101429.
  • Bansal A, Simon MC. Glutathione metabolism in cancer progression and treatment resistance. J Cell Biol. 2018;217(7):2291-2298. doi:10.1083/jcb.201804161.
  • Lv H, Zhen C, Liu J, Yang P, Hu L, Shang P. Unraveling the potential role of glutathione in multiple forms of cell death in cancer therapy. Oxid Med Cell Longev. 2019;2019:3150145. doi:10.1155/2019/3150145
  • Traverso N, Ricciarelli R, Nitti M, et al. Role of glutathione in cancer progression and chemoresistance. Oxid Med Cell Longev. 2013;2013:972913. doi:10.1155/2013/972913.
  • Hayes JD, Dinkova-Kostova AT, Tew KD. Oxidative stress in cancer. Cancer Cell. 2020;38(2):167-197. doi:10.1016/j.ccell.2020.06.001.
  • Ménard C, Martin F, Apetoh L, Bouyer F, Ghiringhelli F. Cancer chemotherapy: not only a direct cytotoxic effect, but also an adjuvant for antitumor immunity. Cancer Immunol Immunother. 2008;57(11):1579-1587. doi:10.1007/s00262-008-0505-6.
  • Singh K, Bhori M, Kasu YA, Bhat G, Marar T. Antioxidants as precision weapons in war against cancer chemotherapy induced toxicity - Exploring the armoury of obscurity. Saudi Pharm J. 2018;26(2):177-190. doi:10.1016/j.jsps.2017.12.013.
  • George S, Abrahamse H. Redox potential of antioxidants in cancer progression and prevention. Antioxidants (Basel). 2020;9(11):1156. doi:10.3390/antiox9111156.
  • Strober, W. Trypan blue exclusion test of cell viability. Curr Protoc Immunol. 1997;21(1): A-3B.
  • Louis KS, Siegel AC: Cell viability analysis using trypan blue: manual and automated methods. In: Stoddart, M. (eds) Mammn Cell Viabil. Methods in Molecular Biology, vol 740. Humana Press. doi:10.1007/978-1-61779-108-6_2
  • Chou TC. Drug combination studies and their synergy quantification using the Chou-Talalay method. Cancer Res. 2010;70(2):440-446. doi:10.1158/0008-5472.CAN-09-1947.
  • Beutler E, Duron O, Kelly BM. Improved method for the determination of blood glutathione. J Lab Clin Med. 1963;61:882-888.
  • Syng-Ai C, Kumari AL, Khar A. Effect of curcumin on normal and tumor cells: role of glutathione and bcl-2. Mol Cancer Ther. 2004;3(9):1101-1108. doi:10.1158/1535-7163.1101.3.9.
  • Erel O. A novel automated method to measure total antioxidant response against potent free radical reactions. Clin Biochem. 2004;37(2):112-119. doi:10.1016/j.clinbiochem.2003.10.014
  • Erel O. A new automated colorimetric method for measuring total oxidant status. Clin Biochem. 2005;38(12):1103-1111. doi:10.1016/j.clinbiochem.2005.08.008
  • Ortega AL, Mena S, Estrela JM. Glutathione in cancer cell death. Cancers (Basel). 2011;3(1):1285-1310. doi:10.3390/cancers3011285
  • Lu SC. Regulation of glutathione synthesis. Mol Aspects Med. 2009;30(1-2):42-59. doi:10.1016/j.mam.2008.05.005.
  • Wu G, Fang YZ, Yang S, Lupton JR, Turner ND. Glutathione metabolism and its implications for health. J Nutr. 2004;134(3):489-492. doi:10.1093/jn/134.3.489.
  • Perry RR, Mazetta JA, Levin M, Barranco SC. Glutathione levels and variability in breast tumors and normal tissue. Cancer. 1993;72(3):783-787. doi:10.1002/1097-0142(19930801)72:3<783::aid-cncr2820720325>3.0.co;2-u
  • Frairia R, Catalano MG, Fortunati N, Fazzari A, Raineri M, Berta L. High energy shock waves (HESW) enhance paclitaxel cytotoxicity in MCF-7 cells. Breast Cancer Res Treat. 2003;81(1):11-19. doi:10.1023/A:1025477421467
  • Ramanathan B, Jan KY, Chen CH, Hour TC, Yu HJ, Pu YS. Resistance to paclitaxel is proportional to cellular total antioxidant capacity. Cancer Res. 2005;65(18):8455-8460. doi:10.1158/0008-5472.CAN-05-1162
  • Alexandre J, Hu Y, Lu W, Pelicano H, Huang P. Novel action of paclitaxel against cancer cells: bystander effect mediated by reactive oxygen species. Cancer Res. 2007;67(8):3512-3517. doi:10.1158/0008-5472.CAN-06-3914.
  • Alexandre J, Batteux F, Nicco C, et al. Accumulation of hydrogen peroxide is an early and crucial step for paclitaxel-induced cancer cell death both in vitro and in vivo. Int J Cancer. 2006;119(1):41-48. doi:10.1002/ijc.21685.
  • Lopaczynski W, Zeisel SH. Antioxidants, programmed cell death, and cancer. Nutr Res. 2001;21(1-2):295-307. doi:10.1016/S0271-5317(00)00288-8.
  • Filomeni G, Graziani I, Rotilio G, Ciriolo MR. trans-Resveratrol induces apoptosis in human breast cancer cells MCF-7 by the activation of MAP kinases pathways. Genes Nutr. 2007;2(3):295-305. doi:10.1007/s12263-007-0059-9.
  • Schnelldorfer T, Gansauge S, Gansauge F, Schlosser S, Beger HG, Nussler AK. Glutathione depletion causes cell growth inhibition and enhanced apoptosis in pancreatic cancer cells. Cancer. 2000;89(7):1440-1447. doi:10.1002/1097-0142(20001001)89:7<1440::AID-CNCR5>3.0.CO;2-0.
  • Jayakumar S, Kunwar A, Sandur SK, Pandey BN, Chaubey RC. Differential response of DU145 and PC3 prostate cancer cells to ionizing radiation: role of reactive oxygen species, GSH and Nrf2 in radiosensitivity. Biochim Biophys Acta. 2014;1840(1):485-494. doi:10.1016/j.bbagen.2013.10.006.
  • Stavrovskaya AA. Cellular mechanisms of multidrug resistance of tumor cells. Biochemistry (Mosc). 2000;65(1):95-106.
  • Mousavi SH, Tavakkol-Afshari J, Brook A, Jafari-Anarkooli I. Direct toxicity of Rose Bengal in MCF-7 cell line: role of apoptosis. Food Chem Toxicol. 2009;47(4):855-859. doi:10.1016/j.fct.2009.01.018.
  • Estrela JM, Ortega A, Mena S, Sirerol JA, Obrador E. Glutathione in metastases: From mechanisms to clinical applications. Crit Rev Clin Lab Sci. 2016;53(4):253-267. doi:10.3109/10408363.2015.1136259.
  • Forman HJ, Zhang H, Rinna A. Glutathione: overview of its protective roles, measurement, and biosynthesis. Mol Aspects Med. 2009;30(1-2):1-12. doi:10.1016/j.mam.2008.08.006.
  • Hadzic T, Aykin-Burns N, Zhu Y, et al. Paclitaxel combined with inhibitors of glucose and hydroperoxide metabolism enhances breast cancer cell killing via H2O2-mediated oxidative stress. Free Radic Biol Med. 2010;48(8):1024-1033. doi:10.1016/j.freeradbiomed.2010.01.018
  • Yang JC, Lu MC, Lee CL, et al. Selective targeting of breast cancer cells through ROS-mediated mechanisms potentiates the lethality of paclitaxel by a novel diterpene, gelomulide K. Free Radic Biol Med. 2011;51(3):641-657. doi:10.1016/j.freeradbiomed.2011.05.012.
  • Zhao MY, Liu P, Sun C, Pei LJ, Huang YG. Propofol augments paclitaxel-ınduced cervical cancer cell ferroptosis ın vitro. Front Pharmacol. 2022;13:816432. doi:10.3389/fphar.2022.816432.
  • Meshkini A, Yazdanparast R. Involvement of oxidative stress in taxol-induced apoptosis in chronic myelogenous leukemia K562 cells. Exp Toxicol Pathol. 2012;64(4):357-365. doi:10.1016/j.etp.2010.09.010.
  • Shen, By., Chen, C., Xu, Yf. et al. Is the combinational administration of doxorubicin and glutathione a reasonable proposal?. Acta Pharmacol Sin 2019;40:699-709. doi:10.1038/s41401-018-0158-8
  • Xu Y, Xin Y, Diao Y, Lu C, Fu J, Luo L, Yin Z. Synergistic effects of apigenin and paclitaxel on apoptosis of cancer cells. PLoS ONE. 2011;6(12):e29169
  • Pan Q, Xue M, Xiao S-s, Wan Y-j, Xu D-b. A combination therapy with baicalein and taxol promotes mitochondria-mediated cell apoptosis: involving in Akt/β-catenin signaling pathway. DNA Cell Biol. 2016;35(11):646–56.
  • Limtrakul P, Khantamat O, Pintha K. Inhibition of P-glycoprotein function and expression by kaempferol and quercetin. J Chemother. 2005;17(1):86–95.
  • Klimaszewska-Wiśniewska A, Hałas-Wiśniewska M, Grzanka A, Grzanka D. Evaluation of anti-metastatic potential of the combination of fisetin with paclitaxel on A549 non-small cell lung cancer cells. Int J Mol Sci. 2018;19(3):661.
  • Zhao J, Li L, Wang Z, Li L, He M, Han S, Dong Y, Liu X, Zhao W, Ke Y. Luteolin attenuates cancer cell stemness in PTX-resistant oesophageal cancer cells through mediating SOX2 protein stability. Pharmacol Res. 2021;174:105939.
  • Alalawy, AI. Key genes and molecular mechanisms related to paclitaxel resistance. Cancer Cell International 2024;24(1):244.doi:10.1186/s12935-024-03415-0.
Toplam 65 adet kaynakça vardır.

Ayrıntılar

Birincil Dil İngilizce
Konular Hücre Gelişimi, Proliferasyon ve Ölümü
Bölüm Araştırma Makalesi
Yazarlar

Gamze Sevri Ekren Aşıcı 0000-0002-9625-7956

İrem Bayar 0000-0002-9363-5085

Adem Yavaş 0000-0003-3506-4306

Ayşegül Bildik 0000-0003-4570-2156

Pınar Alkım Ulutaş 0000-0002-2447-3027

Proje Numarası the project coded VTF-15054
Erken Görünüm Tarihi 24 Aralık 2024
Yayımlanma Tarihi 31 Aralık 2024
Gönderilme Tarihi 1 Ağustos 2024
Kabul Tarihi 15 Aralık 2024
Yayımlandığı Sayı Yıl 2024 Cilt: 10 Sayı: 3

Kaynak Göster

AMA Ekren Aşıcı GS, Bayar İ, Yavaş A, Bildik A, Ulutaş PA. Cytotoxic and antioxidant effects of paclitaxel and glutathione combination on breast cancer cell line. ADYÜ Sağlık Bilimleri Derg. Aralık 2024;10(3):200-210. doi:10.30569/adiyamansaglik.1525999