Antidepressants as additional drugs for human brain gliomas

Revishchin A.V.; Pavlova G.V.

doi:https://doi.org/10.17116/neiro20248806197

Рекомендуем статьи по данной теме:

Связь степени злокачественности и миграционной способности глиом человека с экспрессией изоформ GDNF in vitro. Журнал «Вопросы нейрохирургии» имени Н.Н. Бурденко. 2024;(6):31-38

Глимфатическая система головного мозга в норме и при патологии: нарративный обзор литературы. Журнал «Вопросы нейрохирургии» имени Н.Н. Бурденко. 2025;(4):112-118

Скрининг на мутации TERTp методом цифровой капельной ПЦР коллекции из 52 парных образцов ДНК из плазмы крови и опухолевых тканей пациентов с глиобластомой. Журнал «Вопросы нейрохирургии» имени Н.Н. Бурденко. 2025;(5):87-95

Патогенетические связи гипогонадизма и депрессии у мужчин. Журнал неврологии и психиатрии им. С.С. Корсакова. 2025;(1):17-23

Нейропатическая боль при хронических воспалительных демиелинизирующих полинейропатиях: анализ 64 наблюдений. Российский журнал боли. 2025;(2):45-53

Влияние полиморфных вариантов гена HTR2A на эффективность и безопасность сертралина у больных со смешанным тревожно-депрессивным расстройством. Журнал неврологии и психиатрии им. С.С. Корсакова. 2025;(8):75-84

Психодерматологические аспекты псориаза, современное состояние проблемы. Клиническая дерматология и венерология. 2025;(4):403-411

Модели машинного обучения для дифференциальной диагностики опухолей головного мозга. Профилактическая медицина. 2025;(9):87-93

Окислительный стресс и депрессия при болезни Паркинсона. Журнал неврологии и психиатрии им. С.С. Корсакова. 2025;(9):131-138

Резюме / Abstract:

Глиобластома (ГБ) является наиболее агрессивной злокачественной опухолью головного мозга. На данный момент не найдено оптимального подхода к лечению этого заболевания. Одним из новых направлений терапии стало применение антидепрессантов, у которых обнаружен противоопухолевый эффект. Отличительной особенностью этих препаратов является то, что они давно разрешены для использования и широко применяются в клинической практике для лечения депрессивных состояний.

ЦЕЛЬ ИССЛЕДОВАНИЯ

Анализ данных литературы по механизмам противоопухолевого действия и возможностям применения антидепрессантов при лечении больных с ГБ.

МАТЕРИАЛ И МЕТОДЫ

Проведен поиск в базах данных по ключевым словам: «глиома», «антидепрессанты», «перепрофилирование лекарств».

РЕЗУЛЬТАТЫ

Многочисленные доклинические исследования показали, что на клеточном уровне активность антидепрессантов направлена на усиление апоптоза и аутофагии, торможение клеточного цикла, дифференцировку и/или сохранение стволового статуса клеток, а также на миграцию опухолевых клеток.

ЗАКЛЮЧЕНИЕ

Имеющиеся данные могут служить основанием для продолжения экспериментальных и клинических исследований и поиска терапевтических комбинаций с использованием антидепрессантов для лечения глиомы человека.

Ключевые слова / Keywords:

глиома

антидепрессанты

перепрофилирование лекарств

Авторы / Authors:

Ревищин А.В.

ФГБУН «Институт высшей нервной деятельности и нейрофизиологии Российской академии наук»

SPIN РИНЦ: 8515-7172
Scopus AuthorID: 7003954339
ORCID: 0000-0002-6007-6440

Павлова Г.В.

ФГБУН «Институт высшей нервной деятельности и нейрофизиологии Российской академии наук»;
ФГАУ «НМИЦ нейрохирургии им. акад. Н.Н. Бурденко»

SPIN РИНЦ: 4633-8339
Scopus AuthorID: 7005650683
ORCID: 0000-0002-6885-6601

Дата поступления:

06.09.2024

Дата принятия в печать:

20.09.2024

Закрыть метаданные

Литература / References:

Scannell JW, Blanckley A, Boldon H, Warrington B. Diagnosing the decline in pharmaceutical r&d efficiency. Nature Reviews Drug Discovery. 2012;11:191-200. https://doi.org/10.1038/nrd3681
Hodos RA, Kidd BA, Shameer K, Readhead BP, Dudley JT. In silico methods for drug repurposing and pharmacology. Wiley Interdisciplinary Reviews: Systems Biology and medicine. 2016;8:186-210. https://doi.org/10.1002/wsbm.1337
Zhang Y, Zheng Q, Zhou Y, Liu S. Repurposing clinical drugs as adometdc inhibitors using the scar strategy. Frontiers in Pharmacology. 2020;11:248. https://doi.org/10.3389/fphar.2020.00248
Baker NC, Ekins S, Williams AJ, Tropsha A. A bibliometric review of drug repurposing. Drug Discovery Today. 2018;23:661-672. https://doi.org/10.1016/j.drudis.2018.01.018
King JL, Benhabbour SR. Glioblastoma multiforme-a look at the past and a glance at the future. Pharmaceutics. 2021;13(7):1053. https://doi.org/10.3390/pharmaceutics13071053
Minniti G, Amelio D, Amichetti M, Salvati M, Muni R, Bozzao A, Lanzetta G, Scarpino S, Arcella A, Enrici RM. Patterns of failure and comparison of different target volume delineations in patients with glioblastoma treated with conformal radiotherapy plus concomitant and adjuvant temozolomide. Radiotherapy and Oncology. 2010;97:377-381. https://doi.org/10.1016/j.radonc.2010.08.020
Pinkiewicz M, Pinkiewicz M, Walecki J, Zaczynski A, Zawadzki M. Breaking barriers in neuro-oncology: A scoping literature review on invasive and non-invasive techniques for blood-brain barrier disruption. Cancers. 2024;16(1):236. https://doi.org/10.3390/cancers16010236
van der Meer PB, Dirven L, Hertler C, Boele FW, Batalla A, Walbert T, Rooney AG, Koekkoek JAF. Depression and anxiety in glioma patients. Neuro-Oncology Practice. 2023;10:335-343. https://doi.org/10.1093/nop/npad019
Shi C, Lamba N, Zheng LJ, Cote D, Regestein QR, Liu CM, Tran Q, Routh S, Smith TR, Mekary RA, Broekman MLD. Depression and survival of glioma patients: A systematic review and meta-analysis. Clinical Neurology and Neurosurgery. 2018;172:8-19. https://doi.org/10.1016/j.clineuro.2018.06.016
Tan SK, Jermakowicz A, Mookhtiar AK, Nemeroff CB, Schurer SC, Ayad NG. Drug repositioning in glioblastoma: A pathway perspective. Frontiers in Pharmacology. 2018;9:218. https://doi.org/10.3389/fphar.2018.00218
Gillman PK. Tricyclic antidepressant pharmacology and therapeutic drug interactions updated. British Journal of Pharmacology. 2007;151:737-748. https://doi.org/10.1038/sj.bjp.0707253
Jeon SH, Kim SH, Kim Y, Kim YS, Lim Y, Lee YH, Shin SY. The tricyclic antidepressant imipramine induces autophagic cell death in u-87mg glioma cells. Biochemical and Biophysical Research Communications. 2011;413:311-317. https://doi.org/10.1016/j.bbrc.2011.08.093
Hsu FT, Chiang IT, Wang WS. Induction of apoptosis through extrinsic/intrinsic pathways and suppression of erk/nf-kappab signalling participate in anti-glioblastoma of imipramine. Journal of Cellular and Molecular Medicine. 2020;24:3982-4000. https://doi.org/10.1111/jcmm.15022
Wang Y, Wang X, Wang X, Wu D, Qi J, Zhang Y, Wang K, Zhou D, Meng QM, Nie E, Wang Q, Yu RT, Zhou XP. Imipramine impedes glioma progression by inhibiting yap as a hippo pathway independent manner and synergizes with temozolomide. Journal of Cellular and Molecular Medicine. 2021;25:9350-9363. https://doi.org/10.1111/jcmm.16874
Alburquerque-Gonzalez B, Bernabe-Garcia M, Montoro-Garcia S, Bernabe-Garcia A, Rodrigues PC, Ruiz Sanz J, Lopez-Calderon FF, Luque I, Nicolas FJ, Cayuela ML, Salo T, Perez-Sanchez H, Conesa-Zamora P. New role of the antidepressant imipramine as a fascin1 inhibitor in colorectal cancer cells. Experimental and Molecular Medicine. 2020;52:281-292. https://doi.org/10.1038/s12276-020-0389-x
Histological and clinical effects of imipramine in the treatment of patients with cancer over-expressing fascin1. European Union Clinical Trials Register, 2021. https://www.clinicaltrialsregister.eu/ctr-search/search?query=HITCLIF
Zhang H, Cong QX, Zhang SG, Zhai XW, Li HF, Li SQ. High expression levels of fascin-1 protein in human gliomas and its clinical relevance. Open Medicine (Wars). 2018;13:544-550. https://doi.org/10.1515/med-2018-0080
Munson JM, Fried L, Rowson SA, Bonner MY, Karumbaiah L, Diaz B, Courtneidge SA, Knaus UG, Brat DJ, Arbiser JL, Bellamkonda RV. Anti-invasive adjuvant therapy with imipramine blue enhances chemotherapeutic efficacy against glioma. Science Translational Medicine. 2012;4:127ra136. https://doi.org/10.1126/scitranslmed.3003016
Kolesnikova V, Revishchin A, Fab L, Alekseeva A, Ryabova A, Pronin I, Usachev DY, Kopylov A, Pavlova G. Gqicombi application to subdue glioma via differentiation therapy. Frontiers in Oncology. 2024;14:1322795. https://doi.org/10.3389/fonc.2024.1322795
Pavlova G, Kolesnikova V, Samoylenkova N, Drozd S, Revishchin A, Shamadykova D, Usachev DY, Kopylov A. A combined effect of g-quadruplex and neuro-inducers as an alternative approach to human glioblastoma therapy. Frontiers in Oncology. 2022;12:880740. https://doi.org/10.3389/fonc.2022.880740
Bielecka-Wajdman AM, Lesiak M, Ludyga T, Sieron A, Obuchowicz E. Reversing glioma malignancy: A new look at the role of antidepressant drugs as adjuvant therapy for glioblastoma multiforme. Cancer Chemotherapy and Pharmacology. 2017;79:1249-1256. https://doi.org/10.1007/s00280-017-3329-2
Chryplewicz A, Scotton J, Tichet M, Zomer A, Shchors K, Joyce JA, Homicsko K, Hanahan D. Cancer cell autophagy, reprogrammed macrophages, and remodeled vasculature in glioblastoma triggers tumor immunity. Cancer Cell. 2022;40(10):1111-1127.e9. https://doi.org/10.1016/j.ccell.2022.08.014
Troib A, Azab AN. Effects of psychotropic drugs on nuclear factor kappa b. European Reviews for Medical and Pharmacological Sciences. 2015;19:1198-1208.
Parker KA, Pilkington GJ. Apoptosis of human malignant glioma-derived cell cultures treated with clomipramine hydrochloride, as detected by annexin-v assay. Radiology and Oncology. 2006;40. (2). Retrieved from https://www.radioloncol.com/index.php/ro/article/view/1265
Bilir A, Erguven M, Yazihan N, Aktas E, Oktem G, Sabanci A. Enhancement of vinorelbine-induced cytotoxicity and apoptosis by clomipramine and lithium chloride in human neuroblastoma cancer cell line sh-sy5y. Journal of Neurooncology. 2010;100:385-395. https://doi.org/10.1007/s11060-010-0209-6
Xia Z, Depierre JW, Nassberger L. The tricyclic antidepressants clomipramine and citalopram induce apoptosis in cultured human lymphocytes. Journal of Pharmacy and Pharmacology. 1996;48:115-116. https://doi.org/10.1111/j.2042-7158.1996.tb05889.x
Pollard SM, Yoshikawa K, Clarke ID, Danovi D, Stricker S, Russell R, Bayani J, Head R, Lee M, Bernstein M, Squire JA, Smith A, Dirks P. Glioma stem cell lines expanded in adherent culture have tumor-specific phenotypes and are suitable for chemical and genetic screens. Cell Stem Cell. 2009;4:568-580. https://doi.org/10.1038/bjc.2016.109
Sarrouilhe D, Mesnil M. Serotonin and human cancer: A critical view. Biochimie. 2019;161:46-50. https://doi.org/10.1016/j.biochi.2018.06.016
Cheer SM, Goa KL. Fluoxetine: A review of its therapeutic potential in the treatment of depression associated with physical illness. Drugs. 2001;61:81-110. https://doi.org/10.2165/00003495-200161010-00010
Song T, Li H, Tian Z, Xu C, Liu J, Guo Y. Disruption of nf-kappab signaling by fluoxetine attenuates mgmt expression in glioma cells. OncoTargets and Therapy. 2015;8:2199-2208. https://doi.org/10.2147/OTT.S85948
Ma J, Yang YR, Chen W, Chen MH, Wang H, Wang XD, Sun LL, Wang FZ, Wang DC. Fluoxetine synergizes with temozolomide to induce the chop-dependent endoplasmic reticulum stress-related apoptosis pathway in glioma cells. Oncology Reports. 2016;36:676-684. https://doi.org/10.3892/or.2016.4860
Hosseinimehr SJ, Najafi SH, Shafiee F, Hassanzadeh S, Farzipour S, Ghasemi A, Asgarian-Omran H. Fluoxetine as an antidepressant medicine improves the effects of ionizing radiation for the treatment of glioma. Journal of Bioenergetics and Biomembranes. 2020;52:165-174. https://doi.org/10.1007/s10863-020-09833-9
Bi J, Khan A, Tang J, Armando AM, Wu S, Zhang W, Gimple RC, Reed A, Jing H, Koga T, Wong IT, Gu Y, Miki S, Yang H, Prager B, Curtis EJ, Wainwright DA, Furnari FB, Rich JN, Cloughesy TF, Kornblum HI, Quehenberger O, Rzhetsky A, Cravatt BF, Mischel PS. Targeting glioblastoma signaling and metabolism with a re-purposed brain-penetrant drug. Cell Reports. 2021;37:109957. https://doi.org/10.1016/j.celrep.2021.109957
Tzadok S, Beery E, Israeli M, Uziel O, Lahav M, Fenig E, Gil-Ad I, Weizman A, Nordenberg J. In vitro novel combinations of psychotropics and anti-cancer modalities in u87 human glioblastoma cells. International Journal of Oncology. 2010;37:1043-1051. https://doi.org/10.3892/ijo_00000756
Xu D, Wang C, Zhu X, Zhao W, Jiang B, Cui S, Sun Y, Cui Z. The antidepressant-like effects of fluvoxamine in mice involve the mtor signaling in the hippocampus and prefrontal cortex. Psychiatry Research. 2020;285:112708. https://doi.org/10.1016/j.psychres.2019.112708
Hayashi K, Michiue H, Yamada H, Takata K, Nakayama H, Wei FY, Fujimura A, Tazawa H, Asai A, Ogo N, Miyachi H, Nishiki T, Tomizawa K, Takei K, Matsui H. Fluvoxamine, an anti-depressant, inhibits human glioblastoma invasion by disrupting actin polymerization. Scientific Reports. 2016;6:23372. https://doi.org/10.1038/srep23372
Thakerar A, Simadri K, Alexander M, Fullerton S. Paroxetine for the treatment of intractable and persistent cough in patients diagnosed with cancer. Journal of Oncology Pharmacy Practice. 2019;26:803-808. https://doi.org/10.1177/1078155219870594
Levkovitz Y, Gil-Ad I, Zeldich E, Dayag M, Weizman A. Differential induction of apoptosis by antidepressants in glioma and neuroblastoma cell lines: Evidence for p-c-jun, cytochrome c, and caspase-3 involvement. Journal of Molecular Neuroscience. 2005;27:29-42. https://doi.org/10.1385/JMN:27:1:029
Woroniecka KI, Rhodin KE, Chongsathidkiet P, Keith KA, Fecci PE. T-cell dysfunction in glioblastoma: Applying a new framework. Clinical Cancer Research. 2018;24:3792-3802. https://doi.org/10.1158/1078-0432.CCR-18-0047
Wang T, Zhang H, Han Y, Zheng Q, Liu H, Han M, Li Z. Reversing t cell dysfunction to boost glioblastoma immunotherapy by paroxetine-mediated grk2 inhibition and blockade of multiple checkpoints through biomimetic nanoparticles. Advanced Science. 2023;10:e2204961. https://doi.org/10.1002/advs.202204961
Cantoni GL. The nature of the active methyl donor formed enzymatically from l-methionine and adenosinetriphosphate1,2. Journal of the American Chemical Society. 1952;74(11):2942-2943.
Bottiglieri T, Laundy M, Martin R, Carney MW, Nissenbaum H, Toone BK, Johnson AL, Reynolds EH. S-adenosylmethionine influences monoamine metabolism. Lancet. 1984;2:224. https://doi.org/10.1016/s0140-6736(84)90507-5
Janicak PG, Lipinski J, Davis JM, Altman E, Sharma RP. Parenteral s-adenosyl-methionine (same) in depression: Literature review and preliminary data. Psychopharmacology Bulletin. 1989;25:238-242.
Mosca L, Pagano C, Tranchese RV, Grillo R, Cadoni F, Navarra G, Coppola L, Pagano M, Mele L, Cacciapuoti G, Laezza C, Porcelli M. Antitumoral activity of the universal methyl donor s-adenosylmethionine in glioblastoma cells. Molecules. 2024;29(8):1708. https://doi.org/10.3390/molecules29081708
Linde K, Berner M, Egger M, Mulrow C. St john’s wort for depression: Meta-analysis of randomised controlled trials. The British Journal of Psychiatry. 2005;186:99-107. https://doi.org/10.1192/bjp.186.2.99
Dong X, Zeng Y, Zhang Z, Fu J, You L, He Y, Hao Y, Gu Z, Yu Z, Qu C, Yin X, Ni J, Cruz LJ. Hypericin-mediated photodynamic therapy for the treatment of cancer: A review. Journal of Pharmacy and Pharmacology. 2021;73:425-436. https://doi.org/10.1093/jpp/rgaa018
Couldwell WT, Surnock AA, Tobia AJ, Cabana BE, Stillerman CB, Forsyth PA, Appley AJ, Spence AM, Hinton DR, Chen TC. A phase 1/2 study of orally administered synthetic hypericin for treatment of recurrent malignant gliomas. Cancer. 2011;117:4905-4915. https://doi.org/10.1002/cncr.26123
Ghiasvand S, Javidi MA, Mohammadian A, Mousavi SA, Shahriari F, Alavian F. Transcriptome analysis evinces anti-neoplastic mechanisms of hypericin: A study on u87 glioblastoma cell line. Life Sciences. 2021;266:118874. https://doi.org/10.1016/j.lfs.2020.118874
Doroshenko A, Tomkova S, Kozar T, Stroffekova K. Hypericin, a potential new bh3 mimetic. Frontiers in Pharmacology. 2022;13:991554. https://doi.org/10.3389/fphar.2022.991554
Hovan A, Pevna V, Huntosova V, Miskovsky P, Bano G. Singlet oxygen lifetime changes in dying glioblastoma cells. Photochemistry and Photobiology. 2024;100:159-171. https://doi.org/10.1111/php.13828
Han Y, Chen J, Zou D, Zheng P, Li Q, Wang H, Li P, Zhou X, Zhang Y, Liu Y, Xie P. Efficacy of ketamine in the rapid treatment of major depressive disorder: A meta-analysis of randomized, double-blind, placebo-controlled studies. Neuropsychiatric Disease and Treatment. 2016;12:2859-2867. https://doi.org/10.2147/NDT.S117146
Niwa H, Furukawa KI, Seya K, Hirota K. Ketamine suppresses the proliferation of rat c6 glioma cells. Oncology Letters. 2017;14:4911-4917. https://doi.org/10.3892/ol.2017.6806
Edstrom S, Hellquist BN, Sandstrom M, Sadanandan SA, Bjorkblom B, Melin B, Sjoberg RL. Antidepressants and survival in glioma-a registry-based retrospective cohort study. Neuro-Oncology Practice. 2024;11:125-131. https://doi.org/10.1093/nop/npad057
Seliger C, Oppong FB, Lefranc F, Chinot O, Stupp R, Nabors B, Gorlia T, Weller M. Association of antidepressant drug use with outcome of patients with glioblastoma. International Journal of Cancer. 2023;152:1348-1359. https://doi.org/10.1002/ijc.34344