Research Article
Year 2025,
Volume: 52 Issue: 1, 87 - 94, 14.03.2025
Abstract
References
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- 2.Siegel RL, Giaquinto AN, Jemal A. Cancer statistics.CA Cancer J Clin. 2024; 74(1):12–49.
- 3.Lee AM, Weaver AN, Acosta P, et al. Review ofCurrent and Future Medical Treatments in Head and Neck Squamous Cell Carcinoma. Cancers (Basel).2024; 16(20):3488.
- 4.Vakili S, Behrooz AB, Whichelo R, et al. Progress inPrecision Medicine for Head and Neck Cancer.Cancers (Basel). 2024; 16(21):3716.
- 5.Hua Y, Dai X, Xu Y, et al. Drug repositioning:Progress and challenges in drug discovery forvarious diseases. Eur J Med Chem. 2022;234:114239.
- 6.Linton S, Hossenbaccus L, Ellis AK. Evidence-based use of antihistamines for treatment of allergicconditions. Ann Allergy Asthma Immunol. 2023;131(4):412–20.
- 7.Chen S, Luster AD. Antihistamines for cancerimmunotherapy: More than just treating allergies.Cancer Cell. 2022; 40(1):9–11.
- 8.Tsai MJ, Chang WA, Chuang CH, et al. CysteinylLeukotriene Pathway and Cancer. Int J Mol Sci. 2021; 23(1):120.
- 9.Vivithanaporn P, Sriwantana T, KrueaprasertkulK, et al. Differential effects of montelukast andzafirlukast on MDA-MB-231 triple-negative breastcancer cells: Cell cycle regulation, apoptosis,autophagy, DNA damage and endoplasmic reticulum stress. Mol Med Rep. 2024; 30(2):141.
- 10.Ju S, Singh MK, Han S, et al. Oxidative Stress andCancer Therapy: Controlling Cancer Cells UsingReactive Oxygen Species. Int J Mol Sci. 2024;25(22):12387.
- 11.Arai J, Goto K, Otoyama Y, et al. Leukotrienereceptor antagonists enhance HCC treatmentefficacy by inhibiting ADAMs and suppressing MICAshedding. Cancer Immunol Immunother. 2021;70(1):203–13.
- 12.Zappavigna S, Cossu AM, Grimaldi A, et al. Anti-Inflammatory Drugs as Anticancer Agents. Int J MolSci. 2020; 21(7):2605.
- 13.Doostmohammadi A, Jooya H, Ghorbanian K, etal. Potentials and future perspectives of multi-target drugs in cancer treatment: the next generation anti-cancer agents.Cell Commun Signal. 2024; 22(1):228.
- 14.Tsai MJ, Chang WA, Tsai PH, et al. MontelukastInduces Apoptosis-Inducing Factor-Mediated CellDeath of Lung Cancer Cells. Int J Mol Sci. 2017;18(7):1353.
- 15.Gelzinis JA, Szahaj MK, Bekendam RH, et al.Targeting thiol isomerase activity with zafirlukast to treat ovarian cancer from the bench to clinic. TheFASEB J. 2023; 37(5).
- 16.Bellamkonda K, Satapathy SR, Douglas D, et al.Montelukast, a CysLT1 receptor antagonist, reducescolon cancer stemness and tumor burden in a mouse xenograft model of human colon cancer. Cancer Lett. 2018; 437:13–24.
- 17.Fei Z, Zhang L, Wang L, et al. Montelukastameliorated pemetrexed-induced cytotoxicity inhepatocytes by mitigating endoplasmic reticulum(ER) stress and nucleotide oligomerization domain-like receptor protein 3 (NLRP3) activation.Bioengineered. 2022; 13(3):7894–903.
- 18.Irazoqui AP, Gonzalez A, Buitrago C. Effects ofcalcitriol on the cell cycle of rhabdomyosarcomacells. J Steroid Biochem Mol Biol. 2022; 222:106146.
- 19. Pozzi V, Sartini D, Rocchetti R, et al. Identification and Characterization of Cancer Stem Cells fromHead and Neck Squamous Cell Carcinoma Cell Lines.Cell Physiol Biochem. 2015; 36(2):784–98.
- 20.Yu, S. S., Cirillo, N. The molecular markers ofcancer stem cells in head and neck tumors. J CellPhysiol. 2020 Jan; 235(1):65-73.
- 21.Chen W, Zebaze LN, Dong J, et al. WNK1 kinaseand its partners Akt, SGK1 and NBC-familyNa+/HCO3− cotransporters are potential therapeutic targets for glioblastoma stem-like cells linked to Bisacodyl signaling. Oncotarget. 2018; 9(43):27197–219.
- 22.Xie J, Huang L, Lu YG, et al. Roles of the WntSignaling Pathway in Head and Neck Squamous CellCarcinoma. Front Mol Biosci. 2021; 7.
- 23.Baumeister P, Zhou J, Canis M, et al. Epithelial-to-Mesenchymal Transition-Derived Heterogeneity inHead and Neck Squamous Cell Carcinomas. Cancers(Basel). 2021; 13(21):5355.
- 24.Kang J, Lim H, Lee D, et al. Montelukast inhibitsRANKL-induced osteoclast formation and bone lossvia CysLTR1 and P2Y12. Mol Med Rep. 2018;18(2):2387-2398
- 25.Tong J, Yu Q, Xu W, et al. Montelukast enhancescytocidal effects of carfilzomib in multiple myelomaby inhibiting mTOR pathway. Cancer Biol Ther.2019; 20(3):381–90.
- 26.Zovko A, Yektaei-Karin E, Salamon D, et al.Montelukast, a cysteinyl leukotriene receptorantagonist, inhibits the growth of chronic myeloidleukemia cells through apoptosis. Oncol Rep. 2018;40(2):902-908.
- 27. Piromkraipak P, Parakaw T, Phuagkhaopong S, et al. Cysteinyl leukotriene receptor antagonistsinduce apoptosis and inhibit proliferation of humanglioblastoma cells by downregulating B-celllymphoma 2 and inducing cell cycle arrest. Can JPhysiol Pharmacol. 2018; 96(8):798–806.
- 28. Chen Y, Zhang J, Wei S. Montelukast Inhibits Lung Cancer Cell Migration by Suppressing CysteinylLeukotriene Receptor 1 Expression In vitro. CurrPharm Biotechnol. 2023; 24(10):1335–42.
Year 2025,
Volume: 52 Issue: 1, 87 - 94, 14.03.2025
Abstract
Objective: Head and neck squamous cell carcinoma (HNSCCs) are one of the most common cancer types worldwide. There are different treatment approaches including drug repurposing against HNSCCs. In this study, we aim to evaluate montelukast effect on HNSCC cell lines by proliferative capacity, self-renewal potential, and cell cycle dynamics.
Methods: In the study, UM-SCC-47 and HSC-3 cell lines were cultured and treated with 10 uM montelukast. Control and treated cells investigated by colony formation assay, sphere formation assay. Stemness-related markers were detected via qRT-PCR and cell cycle analysis was performed with flow cytometry.
Results: The sphere formation assay demonstrated that the montelukast treated group was smaller and organized compared to the control. NANOG and SOX2 mRNA levels were reduced whereas KLF4 and OCT3/4 increased. Colony formation was reduced in the montelukast treated group. Cell cycle was arrested in the S phase in montelukast-treated HNSCC groups.
Conclusion: Montelukast treatment at a concentration of 10 μM impacted several functional properties of head and neck cancer cells, highlighting its potential effects in this context. Future studies should explore a broader range of concentrations to better understand its therapeutic potential and dose-dependent effects.
Keywords
Head and Neck Cancer Antihistamine Montelukast Inhibitor of cysteinyl leukotriene receptors Antitumor Effect
References
- 1.Barsouk A, Aluru JS, Rawla P, et al. Epidemiology,Risk Factors, and Prevention of Head and NeckSquamous Cell Carcinoma. Med Sci (Basel). 2023;11(2):42.
- 2.Siegel RL, Giaquinto AN, Jemal A. Cancer statistics.CA Cancer J Clin. 2024; 74(1):12–49.
- 3.Lee AM, Weaver AN, Acosta P, et al. Review ofCurrent and Future Medical Treatments in Head and Neck Squamous Cell Carcinoma. Cancers (Basel).2024; 16(20):3488.
- 4.Vakili S, Behrooz AB, Whichelo R, et al. Progress inPrecision Medicine for Head and Neck Cancer.Cancers (Basel). 2024; 16(21):3716.
- 5.Hua Y, Dai X, Xu Y, et al. Drug repositioning:Progress and challenges in drug discovery forvarious diseases. Eur J Med Chem. 2022;234:114239.
- 6.Linton S, Hossenbaccus L, Ellis AK. Evidence-based use of antihistamines for treatment of allergicconditions. Ann Allergy Asthma Immunol. 2023;131(4):412–20.
- 7.Chen S, Luster AD. Antihistamines for cancerimmunotherapy: More than just treating allergies.Cancer Cell. 2022; 40(1):9–11.
- 8.Tsai MJ, Chang WA, Chuang CH, et al. CysteinylLeukotriene Pathway and Cancer. Int J Mol Sci. 2021; 23(1):120.
- 9.Vivithanaporn P, Sriwantana T, KrueaprasertkulK, et al. Differential effects of montelukast andzafirlukast on MDA-MB-231 triple-negative breastcancer cells: Cell cycle regulation, apoptosis,autophagy, DNA damage and endoplasmic reticulum stress. Mol Med Rep. 2024; 30(2):141.
- 10.Ju S, Singh MK, Han S, et al. Oxidative Stress andCancer Therapy: Controlling Cancer Cells UsingReactive Oxygen Species. Int J Mol Sci. 2024;25(22):12387.
- 11.Arai J, Goto K, Otoyama Y, et al. Leukotrienereceptor antagonists enhance HCC treatmentefficacy by inhibiting ADAMs and suppressing MICAshedding. Cancer Immunol Immunother. 2021;70(1):203–13.
- 12.Zappavigna S, Cossu AM, Grimaldi A, et al. Anti-Inflammatory Drugs as Anticancer Agents. Int J MolSci. 2020; 21(7):2605.
- 13.Doostmohammadi A, Jooya H, Ghorbanian K, etal. Potentials and future perspectives of multi-target drugs in cancer treatment: the next generation anti-cancer agents.Cell Commun Signal. 2024; 22(1):228.
- 14.Tsai MJ, Chang WA, Tsai PH, et al. MontelukastInduces Apoptosis-Inducing Factor-Mediated CellDeath of Lung Cancer Cells. Int J Mol Sci. 2017;18(7):1353.
- 15.Gelzinis JA, Szahaj MK, Bekendam RH, et al.Targeting thiol isomerase activity with zafirlukast to treat ovarian cancer from the bench to clinic. TheFASEB J. 2023; 37(5).
- 16.Bellamkonda K, Satapathy SR, Douglas D, et al.Montelukast, a CysLT1 receptor antagonist, reducescolon cancer stemness and tumor burden in a mouse xenograft model of human colon cancer. Cancer Lett. 2018; 437:13–24.
- 17.Fei Z, Zhang L, Wang L, et al. Montelukastameliorated pemetrexed-induced cytotoxicity inhepatocytes by mitigating endoplasmic reticulum(ER) stress and nucleotide oligomerization domain-like receptor protein 3 (NLRP3) activation.Bioengineered. 2022; 13(3):7894–903.
- 18.Irazoqui AP, Gonzalez A, Buitrago C. Effects ofcalcitriol on the cell cycle of rhabdomyosarcomacells. J Steroid Biochem Mol Biol. 2022; 222:106146.
- 19. Pozzi V, Sartini D, Rocchetti R, et al. Identification and Characterization of Cancer Stem Cells fromHead and Neck Squamous Cell Carcinoma Cell Lines.Cell Physiol Biochem. 2015; 36(2):784–98.
- 20.Yu, S. S., Cirillo, N. The molecular markers ofcancer stem cells in head and neck tumors. J CellPhysiol. 2020 Jan; 235(1):65-73.
- 21.Chen W, Zebaze LN, Dong J, et al. WNK1 kinaseand its partners Akt, SGK1 and NBC-familyNa+/HCO3− cotransporters are potential therapeutic targets for glioblastoma stem-like cells linked to Bisacodyl signaling. Oncotarget. 2018; 9(43):27197–219.
- 22.Xie J, Huang L, Lu YG, et al. Roles of the WntSignaling Pathway in Head and Neck Squamous CellCarcinoma. Front Mol Biosci. 2021; 7.
- 23.Baumeister P, Zhou J, Canis M, et al. Epithelial-to-Mesenchymal Transition-Derived Heterogeneity inHead and Neck Squamous Cell Carcinomas. Cancers(Basel). 2021; 13(21):5355.
- 24.Kang J, Lim H, Lee D, et al. Montelukast inhibitsRANKL-induced osteoclast formation and bone lossvia CysLTR1 and P2Y12. Mol Med Rep. 2018;18(2):2387-2398
- 25.Tong J, Yu Q, Xu W, et al. Montelukast enhancescytocidal effects of carfilzomib in multiple myelomaby inhibiting mTOR pathway. Cancer Biol Ther.2019; 20(3):381–90.
- 26.Zovko A, Yektaei-Karin E, Salamon D, et al.Montelukast, a cysteinyl leukotriene receptorantagonist, inhibits the growth of chronic myeloidleukemia cells through apoptosis. Oncol Rep. 2018;40(2):902-908.
- 27. Piromkraipak P, Parakaw T, Phuagkhaopong S, et al. Cysteinyl leukotriene receptor antagonistsinduce apoptosis and inhibit proliferation of humanglioblastoma cells by downregulating B-celllymphoma 2 and inducing cell cycle arrest. Can JPhysiol Pharmacol. 2018; 96(8):798–806.
- 28. Chen Y, Zhang J, Wei S. Montelukast Inhibits Lung Cancer Cell Migration by Suppressing CysteinylLeukotriene Receptor 1 Expression In vitro. CurrPharm Biotechnol. 2023; 24(10):1335–42.
There are 28 citations in total.
Details
| Primary Language | English |
|---|---|
| Subjects | Health Care Administration, Medical Education, Health Services and Systems (Other) |
| Journal Section | Original Articles |
| Authors | |
| Publication Date | March 14, 2025 |
| Submission Date | January 30, 2025 |
| Acceptance Date | March 3, 2025 |
| Published in Issue | Year 2025 Volume: 52 Issue: 1 |
