Cytodestructive Effects of Photodynamic Exposure in Primary Cultures of Malignant Glioma Cells
DOI:
https://doi.org/10.20535/ibb.2024.8.4.317985Keywords:
malignant glioma, continued growth, primary cultures, photodynamic therapy, chlorine E6, laser irradiation, mitotic indexAbstract
Background. Photodynamic therapy (PDT) is a promising adjuvant method for the treatment of malignant gliomas (MG), including tumors with continued growth and tumor recurrences. For the clinical application of PDT, it is important to substantiate the effectiveness of the cytodestructive effect of the combined use of laser irradiation (LI) and photosensitizer (PS).
Objective. To evaluate the cytodestructive effects of photodynamic exposure with the use of PS chlorine E6 on primary MG cell cultures.
Methods. Primary cell cultures were obtained from samples of biopsy material from patients (n = 6) with a verified diagnosis: 3 primary tumors (1 case of diffuse astrocytoma, NOS (G3), 1 – glioblastoma (GB), NOS (G4), 1 – gliosarcoma (G4)) and 3 – with continued tumor growth (1 – diffuse astrocytoma, NOS (G3), 1 – oligodendroglioma, NOS (G3) and 1 – GB, NOS (G4). Groups of cell cultures included: 1) control – cultured in a standard nutrient medium and experimental; 2) cultured with the addition of chlorine E6 (2.0 mg/ml); 3) cultivated without the addition of PS and subjected to LI; 4) cultivated with the addition of chlorine E6 and subsequent exposure to LI. After 24 h, morphological and morphometric studies were carried out.
Results. The primary MG cultures were characterized by different growth dynamics; mitotic activity of tumor cells varied from the highest rate in the culture of primary GB to lower values – in cultures of recurrent GB and primary astrocytoma and gliosarcoma, and the lowest – in cultures of continued growth of astrocytoma and oligodendroglioma after combined treatment. Direct exposure to chlorine E6 and LI reduced the total number of cells in the culture and their mitotic activity. The greatest cytodestructive effect was achieved with the combined effect of chlorine E6 and LI: the effective dose in the case of primary astrocytoma cells is 10 J/cm2 in pulse mode; for cells of primary GB and gliosarcoma, recurrent astrocytoma and oligodendroglioma, the effective dose is 25 J/cm2 in pulsed mode. In the case of GB cells, continued growth, a dose of 25 J/cm2 is effective for both continuous and pulsed modes of LI.
Conclusions. Primary cell cultures of MG obtained directly from tumor tissue are an adequate model for evaluating the effectiveness of the cytodestructive effect of the combined use of LI and PS for PDT.
References
Fedorenko Z, Goulak L, Gorokh Y, Ryzhov A, Soumkina O. Cancer in Ukraine, 2021-2022: Incidence, mortality, prevalence and other relevant statistics. Bulletin of the National Cancer Registry of Ukraine. 2023;24. Available from: http://ncru.inf.ua/publications/BULL_24/PDF_E/bull_eng_24.pdf
Low JT, Ostrom QT, Cioffi G, Neff C, Waite KA, Kruchko C, et al. Primary brain and other central nervous system tumors in the United States (2014-2018): A summary of the CBTRUS statistical report for clinicians. Neuro-Oncology Practice. 2022 Feb 22;9(3):165-82. DOI: 10.1093/nop/npac015
Louis DN, Perry A, Wesseling P, Brat DJ, Cree IA, Figarella-Branger D, et al. The 2021 WHO Classification of Tumors of the Central Nervous System: a summary. Neuro-Oncology. 2021;23(8):1231-51. DOI: 10.1093/neuonc/noab106
Ostrom QT, Price M, Neff C, Cioffi G, Waite KA, Kruchko C, et al. CBTRUS Statistical Report: Primary brain and other central nervous system tumors diagnosed in the United States in 2016-2020. Neuro-Oncology. 2023 Oct 4;25(Supplement_4):iv1-iv99. DOI: 10.1093/neuonc/noad149
Dupont C, Vermandel M, Leroy H-A, Quidet M, Lecomte F, Delhem N, et al. INtraoperative photoDYnamic Therapy for GliOblastomas (INDYGO): Study Protocol for a Phase I Clinical Trial. Neurosurgery. 2019 Jun 1;84(6):E414-E419. DOI: 10.1093/neuros/nyy324
van Solinge TS, Nieland L, Chiocca EA, Broekman MLD. Advances in local therapy for glioblastoma - taking the fight to the tumour. Nat Rev Neurol. 2022;18(4):221-36. DOI: 10.1038/s41582-022-00621-0
Muragaki Y, Akimoto J, Maruyama T, Iseki H, Ikuta S, Nitta M, et al. Phase II clinical study on intraoperative photodynamic therapy with talaporfin sodium and semiconductor laser in patients with malignant brain tumors. J Neurosurg. 2013 Oct;119(4):845-52. DOI: 10.3171/2013.7.JNS13415
Quirk BJ, Brandal G, Donlon S, Vera JC, Mang TS, Foy AB, et al. Photodynamic therapy (PDT) for malignant brain tumors--where do we stand? Photodiagnosis Photodyn Ther. 2015 Sep;12(3):530-44. DOI: 10.1016/j.pdpdt.2015.04.009
Abdel Gaber SA, Müller P, Zimmermann W, Hüttenberger D, Wittig R, Abdel Kader MH, et al. ABCG2-mediated suppression of chlorin e6 accumulation and photodynamic therapy efficiency in glioblastoma cell lines can be reversed by KO143. J Photochem Photobiol B. 2018 Jan;178:182-91. DOI: 10.1016/j.jphotobiol.2017.10.035
Domka W, Bartusik-Aebisher D, Rudy I, Dynarowicz K, Pięta K, Aebisher D. Photodynamic therapy in brain cancer: mechanisms, clinical and preclinical studies and therapeutic challenges. Front Chem. 2023;11:1250621. DOI: 10.3389/fchem.2023.1250621
Hsia T, Small JL, Yekula A, Batool SM, Escobedo AK, Ekanayake E, et al. Systematic review of photodynamic therapy in gliomas. Cancers. 2023;15(15):3918. DOI: 10.3390/cancers15153918
Aebisher D, Przygórzewska A, Myśliwiec A, Dynarowicz K, Krupka-Olek M, Bożek A, et al. Current photodynamic therapy for glioma treatment: An update. Biomedicines. 2024;12(2):375. DOI: 10.3390/biomedicines12020375
van Linde ME, Brahm CG, de Witt Hamer PC, Reijneveld JC, Bruynzeel AME, Vandertop WP, et al. Treatment outcome of patients with recurrent glioblastoma multiforme: a retrospective multicenter analysis. J Neurooncol. 2017;135(1):183-92. DOI: 10.1007/s11060-017-2564-z
Schipmann S, Müther M, Stögbauer L, Zimmer S, Brokinkel B, Holling M, et al. Combination of ALA-induced fluorescence-guided resection and intraoperative open photodynamic therapy for recurrent glioblastoma: case series on a promising dual strategy for local tumor control. J Neurosurg. 2021;134(2):426-36. DOI: 10.3171/2019.11.JNS192443
Lietke S, Schmutzer M, Schwartz C, Weller J, Siller S, Aumiller M, et al. Interstitial photodynamic therapy using 5-ALA for malignant glioma recurrences. Cancers (Basel). 2021 Apr 7;13(8):1767. DOI: 10.3390/cancers13081767
Vermandel M, Dupont C, Lecomte F, Leroy H-A, Tuleasca C, Mordon S, et al. Standardized intraoperative 5-ALA photodynamic therapy for newly diagnosed glioblastoma patients: a preliminary analysis of the INDYGO clinical trial. J Neurooncol. 2021;152(3):501-14. DOI: 10.1007/s11060-021-03718-6
Kobayashi T, Nitta M, Shimizu K, Saito T, Tsuzuki S, Fukui A, et al. Therapeutic options for recurrent glioblastoma - efficacy of talaporfin sodium mediated photodynamic therapy. Pharmaceutics. 2022;14(2):353. DOI: 10.3390/pharmaceutics14020353
Vilchez ML, Rodríguez LB, Palacios RE, Prucca CG, Caverzán MD, Caputto BL, et al. Isolation and initial characterization of human glioblastoma cells resistant to photodynamic therapy. Photodiagnosis Photodyn Ther. 2021 Mar;33:102097. DOI: 10.1016/j.pdpdt.2020.102097
Ren Z, Wen J, Mo Y, Zhang P, Chen H, Wen J. A systematic review and meta-analysis of fluorescent-guided resection and therapy-based photodynamics on the survival of patients with glioma. Lasers Med Sci. 2022;37(2):789-97. DOI: 10.1007/s10103-021-03426-7
Santos KLM, Barros RM, da Silva Lima DP, Nunes AMA, Sato MR, Faccio R, et al. Prospective application of phthalocyanines in the photodynamic therapy against microorganisms and tumor cells: A mini-review. Photodiagnosis Photodyn Ther. 2020 Dec;32:102032. DOI: 10.1016/j.pdpdt.2020.102032
Leroy H-A, Guérin L, Lecomte F, Baert G, Vignion A-S, Mordon S, et al. Is interstitial photodynamic therapy for brain tumors ready for clinical practice? A systematic review. Photodiagnosis Photodyn Ther. 2021;36:102492. DOI: 10.1016/j.pdpdt.2021.102492
Bartusik-Aebisher D, Żołyniak A, Barnaś E, Machorowska-Pieniążek A, Oleś P, Kawczyk-Krupka A, et al. The use of photodynamic therapy in the treatment of brain tumors - A review of the literature. Molecules. 2022;27(20):6847. DOI: 10.3390/molecules27206847
PubChem Compound Summary for CID 5479494, Chlorin e6. National Center for Biotechnology Information. 2024. Available from: https://pubchem.ncbi.nlm.nih.gov/compound/phytochlorin
Shrestha R, Lee HJ, Lim J, Gurung P, Thapa Magar TB, Kim Y-T, et al. Effect of photodynamic therapy with chlorin e6 on canine tumors. Life. 2022;12(12):2102. DOI: 10.3390/life12122102
Thapa Magar TB, Mallik SK, Gurung P, Lim J, Kim YT, Shrestha R, et al. Chlorin E6-curcumin-mediated photodynamic therapy promotes an anti-photoaging effect in UVB-irradiated fibroblasts. Int J Mol Sci. 2023 Aug 30;24(17):13468. DOI: 10.3390/ijms241713468
Hur G-H, Ryu A-R, Kim Y-W, Lee M-Y. The potential anti-photoaging effect of photodynamic therapy using chlorin e6-curcumin conjugate in UVB-irradiated fibroblasts and hairless mice. Pharmaceutics. 2022;14(5):968. DOI: 10.3390/pharmaceutics14050968
Hak A, Ali MS, Sankaranarayanan SA, Shinde VR, Rengan AK. Chlorin e6: a promising photosensitizer in photo-based cancer nanomedicine. ACS Appl Bio Mater. 2023;6(2):349-64. DOI: 10.1021/acsabm.2c00891
Hamaliya MF, Shyshko YD, Shtonʹ IO, Kholin VV, Shcherbakov OB, Usatenko OV. Photodynamic activity of second-generation photosensitizer fotolon (chlorin e6) and its golden nanocomposite: experiments in vitro and in vivo. Photobiology and Photomedicine. 2012;9(1-2):99-103. Available from: https://periodicals.karazin.ua/photomedicine/article/view/13195
Rozumenko VD, Liubich LD, Staino LP, Egorova DM, Vaslovych VV, Rozumenko AV, et al. Effects of photodynamic exposure using chlorine E6 on U251 glioblastoma cell line in vitro. Ukr Neurosurg J. 2023;29(2):11-21. DOI: 10.25305/unj.273699
Search of: photodynamic therapy | Glioma - List Results. U.S. National Library of Medicine. Available from: https://clinicaltrials.gov/ct2/results?cond=Glioma&term=photodynamic++therapy&cntry=&state=&city=&dist=&Search=Search
Rozumenko VD, Liubich LD, Staino LP, Egorova DM, Dashchakovskyi AV, Vaslovych VV, et al. Comparison of the effects of photodynamic exposure with the use of chlorine E6 on glioblastoma cells of the U251 line and human embryonic kidney cells of the HEK293 line in vitro. Ukr Neurosurg J. 2024;30(3):38-51. DOI: 10.25305/unj.306363
Cramer SW, Chen CC. Photodynamic therapy for the treatment of glioblastoma. Front Surg. 2020;6:81. DOI: 10.3389/fsurg.2019.00081
Dubey SK, Pradyuth SK, Saha RN, Singhvi G, Alexander A, Agrawal M, et al. Application of photodynamic therapy drugs for management of glioma. J Porphyrins Phthalocyanines. 2019;23(11-12):1216-28. DOI: 10.1142/S1088424619300192
Sobhani N, Samadani AA. Implications of photodynamic cancer therapy: an overview of PDT mechanisms basically and practically. J Egypt Natl Canc Inst. 2021;33(1):34. DOI: 10.1186/s43046-021-00093-1
Maharjan PS, Bhattarai HK. Singlet oxygen, photodynamic therapy, and mechanisms of cancer cell death. J Oncol. 2022 Jun 25;2022:7211485. DOI: 10.1155/2022/7211485
Przygoda M, Bartusik-Aebisher D, Dynarowicz K, Cieślar G, Kawczyk-Krupka A, Aebisher D. Cellular mechanisms of singlet oxygen in photodynamic therapy. Int J Mol Sci. 2023;24(23):16890. DOI: 10.3390/ijms242316890
Szewczyk G, Mokrzyński K, Sarna T. Generation of singlet oxygen inside living cells: correlation between phosphorescence decay lifetime, localization and outcome of photodynamic action. Photochem Photobiol Sci. 2024;23(9):1673-85. DOI: 10.1007/s43630-024-00620-8
Li F, Cheng Y, Lu J, Hu R, Wan Q, Feng H. Photodynamic therapy boosts anti-glioma immunity in mice: a dependence on the activities of T cells and complement C3. J Cell Biochem. 2011;112(10):3035-43. DOI: 10.1002/jcb.23228
Kaneko S, Fujimoto S, Yamaguchi H, Yamauchi T, Yoshimoto T, Tokuda K. Photodynamic therapy of malignant gliomas. In: Intracranial Gliomas Part III - Innovative Treatment Modalities, vol. 32. Basel: S. Karger AG, 2018, pp. 1-13. DOI: 10.1159/000469675
Yanovsky RL, Bartenstein DW, Rogers GS, Isakoff SJ, Chen ST. Photodynamic therapy for solid tumors: a review of the literature. Photodermatol Photoimmunol Photomed. 2019;35(5):295-303. DOI: 10.1111/phpp.12489
Márquez J, Alonso FJ, Matés JM, Segura JA, Martín-Rufián M, Campos-Sandoval JA. Glutamine addiction in gliomas. Neurochem Res. 2017;42(6):1735-46. DOI: 10.1007/s11064-017-2212-1
Rivera JF, Sridharan SV, Nolan JK, Miloro SA, Alam MA, Rickus JL, et al. Real-time characterization of uptake kinetics of glioblastoma vs. astrocytes in 2D cell culture using microelectrode array. Analyst. 2018;143(20):4954-66. DOI: 10.1039/c8an01198b
Moan J, Peng Q. An outline of the history of PDT. In: Patrice T, editor. Photodynamic therapy. London: The Royal Society of Chemistry; 2003. p. 1-18. DOI: 10.1039/9781847551658-00001
Mahmoudi K, Garvey KL, Bouras A, Cramer G, Stepp H, Jesu Raj JG, et al. 5-aminolevulinic acid photodynamic therapy for the treatment of high-grade gliomas. J Neurooncol. 2019;141(3):595-607. DOI: 0.1007/s11060-019-03103-4
Senders JT, Muskens IS, Schnoor R, Karhade AV, Cote DJ, Smith TR, et al. Agents for fluorescence-guided glioma surgery: a systematic review of preclinical and clinical results. Acta Neurochir (Wien). 2017;159(1):151-67. DOI: 10.1007/s00701-016-3028-5
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