{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T11:49:12Z","timestamp":1792842552363,"version":"4.5.0"},"reference-count":59,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,1,29]],"date-time":"2024-01-29T00:00:00Z","timestamp":1706486400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Photodynamic therapy (PDT) is a light-based technique used in the treatment of malignant and non-malignant tissue. Aluminium-phthalocyanine chloride tetra sulfonate (AlPcS4Cl)-mediated PDT has been well investigated on several cancer types, including oesophageal cancer. However, the effects of (AlPcS4Cl)-mediated PDT on DNA damage response and the mechanism of cell death in oesophageal cancer needs further investigation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Here, we examined the in vitro effects of AlPcS<jats:sub>4<\/jats:sub>Cl-mediated PDT on cell cycle, DNA damage response, oxidative stress, and intrinsic apoptotic cell death pathway in HKESC-1 oesophageal cancer cells. The HKESC-1 cells were exposed to PDT using a semiconductor laser diode (673.2 nm, 5 J\/cm<jats:sup>2<\/jats:sup> fluency). Cell viability and cytotoxicity were determined by the ATP cell viability assay and the lactate dehydrogenase (LDH) release assay, respectively. Cell cycle and DNA damage response (DDR) analyses were conducted using the Muse\u2122 cell cycle kit and the Muse<jats:sup>\u00ae<\/jats:sup> multi-color DNA damage kit, respectively. The mode of cell death was identified using the Annexin V-FITC\/PI detection assay and Muse\u00ae Autophagy LC3 antibody-based kit. The intrinsic apoptotic pathway was investigated by measuring the cellular reactive oxygen species (ROS) levels, mitochondrial membrane potential (\u0394\u03a8m) function, cytochrome c levels and the activity of caspase 3\/7 enzymes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The results show that AlPcS<jats:sub>4<\/jats:sub>Cl-based PDT reduced cell viability, induced cytotoxicity, cell cycle arrest at the G0\/G1 phase, and DNA double-strand break (DSB) through the upregulation of the ataxia telangiectasia mutated (ATM), a DNA damage sensor. In addition, the findings showed that AlPcS<jats:sub>4<\/jats:sub>Cl-based PDT induced cell death via apoptosis, which is observed through increased ROS production, reduced \u0394\u03a8m, increased cytochrome c release, and activation of caspase 3\/7 enzyme. Finally, no autophagy was observed in the AlPcS<jats:sub>4<\/jats:sub>Cl-mediated PDT-treated cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our findings showed that apoptotic cell death is the main cell death mechanism triggered by AlPcS<jats:sub>4<\/jats:sub>Cl-mediated PDT in oesophageal cancer cells.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fonc.2024.1338802","type":"journal-article","created":{"date-parts":[[2024,1,29]],"date-time":"2024-01-29T04:39:25Z","timestamp":1706503165000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":19,"title":["Aluminium phthalocyanine-mediated photodynamic therapy induces ATM-related DNA damage response and apoptosis in human oesophageal cancer cells"],"prefix":"10.3389","volume":"14","author":[{"given":"Onyisi Christiana","family":"Didamson","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rahul","family":"Chandran","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heidi","family":"Abrahamse","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,1,29]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"649","DOI":"10.1053\/j.gastro.2022.05.054","article-title":"The global landscape of esophageal squamous cell carcinoma and esophageal adenocarcinoma incidence and mortality in 2020 and projections to 2040: New estimates from GLOBOCAN 2020","volume":"163","author":"Morgan","year":"2022","journal-title":"Gastroenterology."},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21660","article-title":"Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"71","author":"Sung","year":"2021","journal-title":"CA Cancer J Clin"},{"key":"B3","article-title":"In vitro effects of aluminium (iii) phthalocyanine chloride tetra sulphonic acid-mediated photodynamic therapy on oesophageal cancer","volume-title":"The 66th annual conference of the South African institute of physics; 2022 4-8th july 2022; virtual","author":"Didamson","year":""},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1016\/j.pdpdt.2008.06.001","article-title":"Photodynamic therapy of early esophageal cancer","volume":"5","author":"Filonenko","year":"2008","journal-title":"Photodiagnosis Photodyn Ther"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1007\/s10388-020-00799-6","article-title":"Evaluation of the efficacy and safety of salvage photodynamic therapy by talaporfin sodium for cervical esophageal cancers and lesions larger than 3 cm","volume":"18","author":"Hayashi","year":"2021","journal-title":"Esophagus."},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.5946\/ce.2020.073","article-title":"Photodynamic therapy for esophageal cancer","volume":"54","author":"Inoue","year":"2021","journal-title":"Clin Endosc."},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.3390\/jcm9051509","article-title":"Photodynamic therapy using talaporfin sodium for local failure after chemoradiotherapy or radiotherapy for esophageal cancer: A single center experience","volume":"9","author":"Ishida","year":"2020","journal-title":"J Clin Med"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2018.07.049","article-title":"Photodynamic therapy \u2013 mechanisms, photosensitizers and combinations","volume":"106","author":"Kwiatkowski","year":"2018","journal-title":"Biomedicine pharmacotherapy = Biomedecine pharmacotherapie."},{"key":"B9","doi-asserted-by":"publisher","first-page":"455","DOI":"10.1038\/s41419-022-04851-4","article-title":"Which cell death modality wins the contest for photodynamic therapy of cancer","volume":"13","author":"Mishchenko","year":"2022","journal-title":"Cell Death Dis"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1111\/php.12857","article-title":"Cell death pathways associated with photodynamic therapy: An update","volume":"94","author":"Kessel","year":"2018","journal-title":"Photochem Photobiol Sci"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.14029","article-title":"Multicenter phase II study of salvage photodynamic therapy using talaporfin sodium (ME2906) and a diode laser (PNL6405EPG) for local failure after chemoradiotherapy or radiotherapy for esophageal cancer","volume":"8","author":"Yano","year":"2017","journal-title":"Oncotarget"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1007\/s10388-023-01020-0","article-title":"The feasibility of post-photodynamic therapy salvage esophagectomy in patients with esophageal squamous cell carcinoma treated with definitive chemoradiotherapy","volume":"20","author":"Shigeno","year":"2023","journal-title":"Esophagus."},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1364\/OE.25.016795","article-title":"Flexible laser endoscope for minimally invasive photodynamic diagnosis (PDD) and therapy (PDT) toward efficient tumor removal","volume":"25","author":"Hu","year":"2017","journal-title":"Opt Express."},{"key":"B14","doi-asserted-by":"publisher","first-page":"0907202","DOI":"10.3788\/CJL221218","article-title":"Development and clinical application of endoscopic techniques in photodynamic therapy for luminal tumors","volume":"50","author":"Zhao","year":"2023","journal-title":"Chin J Lasers."},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1111\/1759-7714.13223","article-title":"Clinical application of photodynamic therapy for Malignant airway tumors in China","volume":"11","author":"Jin","year":"2020","journal-title":"Thorac Cancer."},{"key":"B16","doi-asserted-by":"publisher","first-page":"1943","DOI":"10.3390\/pharmaceutics13111943","article-title":"Targeted photodynamic diagnosis and therapy for esophageal cancer: Potential role of functionalized nanomedicine","volume":"13","author":"Didamson","year":"2021","journal-title":"Pharmaceutics."},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1089\/pho.2008.2321","article-title":"The effects of two metallophthalocyanines on the viability and proliferation of an esophageal cancer cell line","volume":"27","author":"Kresfelder","year":"2009","journal-title":"Photomed Laser Surg"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.3892\/ijo.2017.3854","article-title":"Novel zinc phthalocyanine as a promising photosensitizer for photodynamic treatment of esophageal cancer","volume":"50","author":"Kuzyniak","year":"2017","journal-title":"Int J Oncol"},{"key":"B19","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1016\/j.jphotobiol.2005.12.004","article-title":"The effect of Ge, Si and Sn phthalocyanine photosensitizers on cell proliferation and viability of human oesophageal carcinoma cells","volume":"83","author":"Seotsanyana-Mokhosi","year":"2006","journal-title":"J Photochem Photobiol B"},{"key":"B20","doi-asserted-by":"publisher","first-page":"96","DOI":"10.1016\/j.jphotobiol.2019.03.018","article-title":"Effect of dose responses of hydrophilic aluminium (III) phthalocyanine chloride tetrasulphonate based photosensitizer on lung cancer cells","volume":"194","author":"Crous","year":"2019","journal-title":"J Photochem Photobiol B"},{"key":"B21","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1186\/s12951-015-0095-3","article-title":"Aluminum-phthalocyanine chloride-based photodynamic therapy inhibits PI3K\/Akt\/Mtor pathway in oral squamous cell carcinoma cells in vitro","volume":"1","author":"Velloso NV, Muehlmann LA, Longo JP, Silva JR, Zancanela DC","year":"2012","journal-title":"Chemotherapy"},{"key":"B22","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1186\/s12951-015-0095-3","article-title":"Aluminium-phthalocyanine chloride nanoemulsions for anticancer photodynamic therapy: Development and in vitro activity against monolayers and spheroids of human mammary adenocarcinoma MCF-7 cells","volume":"13","author":"Muehlmann","year":"2015","journal-title":"J Nanobiotechnology."},{"key":"B23","doi-asserted-by":"publisher","first-page":"5407012","DOI":"10.1155\/2017\/5407012","article-title":"Susceptibility of in vitro melanoma skin cancer to photoactivated hypericin versus aluminium(III) phthalocyanine chloride tetrasulphonate","volume":"2017","author":"Ndhundhuma","year":"2017","journal-title":"BioMed Res Int"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1016\/S1572-1000(05)00007-4","article-title":"Mechanisms in photodynamic therapy: Part one-photosensitizers, photochemistry and cellular localization","volume":"1","author":"Castano","year":"2004","journal-title":"Photodiagnosis Photodyn Ther"},{"key":"B25","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1016\/j.mla.2011.04.001","article-title":"Subcellular co-localization of aluminum (III) phthalocyanine chloride tetrasulphonate with fluorescent markers in the human melanoma cell-line HT-144","volume":"26","author":"Ndhundhuma","year":"2011","journal-title":"Med laser Appl"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1021\/acsomega.8b00692","article-title":"Targeting of a photosensitizer to the mitochondrion enhances the potency of photodynamic therapy","volume":"3","author":"Mahalingam","year":"2018","journal-title":"ACS Omega."},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2011.05.023","article-title":"Major determinants of photoinduced cell death: Subcellular localization versus photosensitization efficiency","volume":"51","author":"Oliveira","year":"2011","journal-title":"Free Radical Biol Med"},{"key":"B28","doi-asserted-by":"publisher","first-page":"112208","DOI":"10.1016\/j.jphotobiol.2021.112208","article-title":"The localization of the photosensitizer determines the dynamics of the secondary production of hydrogen peroxide in cell cytoplasm and mitochondria","volume":"219","author":"Peskova","year":"2021","journal-title":"J Photochem Photobiol B"},{"key":"B29","doi-asserted-by":"publisher","first-page":"383027","DOI":"10.1155\/2014\/383027","article-title":"Multiorganelle localization of metallated phthalocyanine photosensitizer in colorectal cancer cells (DLD-1 and caCo-2) enhances efficacy of photodynamic therapy","volume":"2014","author":"Sekhejane","year":"2014","journal-title":"Int J Photoenergy."},{"key":"B30","doi-asserted-by":"publisher","first-page":"102645","DOI":"10.1016\/j.pdpdt.2021.102645","article-title":"Chlorin e6 mediated photodynamic therapy triggers resistance through ATM-related DNA damage response in lung cancer cells","volume":"37","author":"Ma","year":"2022","journal-title":"Photodiagnosis Photodyn Ther"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2015.10.040","article-title":"Targeting the DNA damage response in cancer","volume":"60","author":"O\u2019Connor Mark","year":"2015","journal-title":"Mol Cell"},{"key":"B32","article-title":"Cell death response to DNA damage","volume":"92","author":"Wang","year":"2019","journal-title":"Yale J Biol Med"},{"key":"B33","doi-asserted-by":"publisher","first-page":"107391","DOI":"10.1016\/j.pharmthera.2019.07.002","article-title":"ATM in DNA repair in cancer","volume":"203","author":"Jin","year":"2019","journal-title":"Pharmacol Ther"},{"key":"B34","doi-asserted-by":"publisher","first-page":"188757","DOI":"10.1016\/j.bbcan.2022.188757","article-title":"Cancer-associated transcription factors in DNA damage response","volume":"1877","author":"Kciuk","year":"2022","journal-title":"Biochim Biophys Acta Rev Cancer."},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1177\/1535370219826544","article-title":"Genotoxic effects of photodynamic therapy in laryngeal cancer cells - An in vitro study","volume":"244","author":"Dailton Guedes de Oliveira Moraes","year":"2019","journal-title":"Exp Biol Med"},{"key":"B36","doi-asserted-by":"publisher","first-page":"281068","DOI":"10.1155\/2012\/281068","article-title":"Assessment of DNA damage after photodynamic therapy using a metallophthalocyanine photosensitizer","volume":"2012","author":"El-Hussein","year":"2012","journal-title":"Int J Photoenergy."},{"key":"B37","doi-asserted-by":"publisher","first-page":"3288","DOI":"10.3390\/cells11203288","article-title":"In Vitro cell death mechanisms induced by dicoma anomala root extract in combination with ZnPcS4 Mediated-photodynamic therapy in A549 lung cancer cells","volume":"11","author":"Chota","year":"2022","journal-title":"Cells."},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamcr.2016.09.012","article-title":"Activation of apoptosis signalling pathways by reactive oxygen species","volume":"1863","author":"Redza-Dutordoir","year":"2016","journal-title":"Biochim Biophys Acta - Mol Cell Res"},{"key":"B39","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1152\/physrev.00013.2006","article-title":"Mitochondrial membrane permeabilization in cell death","volume":"87","author":"Kroemer","year":"2007","journal-title":"Physiol Rev"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2008.297","article-title":"Caspases in apoptosis and beyond","volume":"27","author":"Li","year":"2008","journal-title":"Oncogene."},{"key":"B41","doi-asserted-by":"publisher","first-page":"3484","DOI":"10.3390\/cancers13143484","article-title":"Light technology for efficient and effective photodynamic therapy: A critical review","volume":"13","author":"Algorri","year":"2021","journal-title":"Cancers."},{"key":"B42","doi-asserted-by":"publisher","first-page":"210148","DOI":"10.1098\/rsos.210148","article-title":"Aluminium (III) phthalocyanine chloride tetrasulphonate is an effective photosensitizer for the eradication of lung cancer stem cells","volume":"8","author":"Crous","year":"2021","journal-title":"R Soc Open Sci"},{"key":"B43","volume-title":"Photodynamic therapy using sulfonated aluminium phthalocyaninemix for the eradication of cervical cancer and cervical cancer stem cells","author":"Chizenga","year":"2018"},{"key":"B44","doi-asserted-by":"publisher","first-page":"74","DOI":"10.1038\/s41580-021-00404-3","article-title":"Cell cycle control in cancer","volume":"23","author":"Matthews","year":"2022","journal-title":"Nat Rev Mol Cell Biol"},{"key":"B45","doi-asserted-by":"publisher","first-page":"199","DOI":"10.3390\/coatings12020199","article-title":"Photodynamic therapy with an alPcS4Cl gold nanoparticle conjugate decreases lung cancer& Metastatic potential","volume":"12","author":"Crous","year":"2022","journal-title":"Coatings."},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.3389\/fnano.2022.928010","article-title":"Zinc phthalocyanine tetrasulfonate-loaded ag@mSiO2 nanoparticles for active targeted photodynamic therapy of colorectal cancer","volume":"4","author":"Montaseri","year":"2022","journal-title":"Front nanotechnol"},{"key":"B47","doi-asserted-by":"publisher","first-page":"98","DOI":"10.1039\/c1pp05190c","article-title":"DNA damage spectra induced by photosensitization","volume":"11","author":"Epe","year":"2012","journal-title":"Photochem Photobiol Sci"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.3390\/cancers15164155","article-title":"Understanding DNA damage response and DNA repair in multiple myeloma","volume":"15","author":"Petrilla","year":"2023","journal-title":"Cancers"},{"key":"B49","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.dnarep.2015.12.009","article-title":"ATM kinase: Much more than a DNA damage responsive protein","volume":"39","author":"Guleria","year":"2016","journal-title":"DNA repair."},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.4161\/cc.9.11.11810","article-title":"Dephosphorylation of \u03b3-H2AX by WIP1: An important homeostatic regulatory event in DNA repair and cell cycle control","volume":"9","author":"Moon","year":"2010","journal-title":"Cell Cycle"},{"key":"B51","doi-asserted-by":"publisher","first-page":"17","DOI":"10.3892\/ol.2023.14150","article-title":"Hematoporphyrin derivative photodynamic therapy induces apoptosis and suppresses the migration of human esophageal squamous cell carcinoma cells by regulating the PI3K\/AKT\/mTOR signaling pathway","volume":"27","author":"Wei","year":"2024","journal-title":"Oncol Lett"},{"key":"B52","doi-asserted-by":"publisher","first-page":"101084","DOI":"10.1016\/j.redox.2018.101084","article-title":"ROS and the DNA damage response in cancer","volume":"25","author":"Srinivas","year":"2019","journal-title":"Redox Biol"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.2174\/1871520621666210608095512","article-title":"Reactive oxygen species (ROS): Key components in cancer therapies","volume":"22","author":"Sahoo","year":"2022","journal-title":"Anticancer Agents Med Chem"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1016\/j.mito.2011.01.010","article-title":"The multiple functions of cytochrome c and their regulation in life and death decisions of the mammalian cell: From respiration to apoptosis","volume":"11","author":"H\u00fcttemann","year":"2011","journal-title":"Mitochondrion."},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1016\/j.bj.2018.05.002","article-title":"Evaluation of cell damage induced by irradiated Zinc-Phthalocyanine-gold dendrimeric nanoparticles in a breast cancer cell line","volume":"41","author":"Mfouo-Tynga","year":"2018","journal-title":"BioMed J"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1016\/j.biocel.2013.08.012","article-title":"Lysosomal and mitochondrial permeabilization mediates zinc(II) cationic phthalocyanine phototoxicity","volume":"45","author":"Marino","year":"2013","journal-title":"Int J Biochem Cell Biol"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1007\/s10495-018-01512-w","article-title":"Oxidative stress generated by irradiation of a zinc(II) phthalocyanine induces a dual apoptotic and necrotic response in melanoma cells","volume":"24","author":"Valli","year":"2019","journal-title":"Apoptosis."},{"key":"B58","doi-asserted-by":"publisher","first-page":"a008656","DOI":"10.1101\/cshperspect.a008656","article-title":"Caspase functions in cell death and disease","volume":"5","author":"McIlwain","year":"2013","journal-title":"Cold Spring Harb Perspect Biol"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2020.01.018","article-title":"Crosstalk between oxidative stress-induced apoptotic and autophagic signaling pathways in Zn(II) phthalocyanine photodynamic therapy of melanoma","volume":"152","author":"Valli","year":"2020","journal-title":"Free Radic Biol Med"}],"container-title":["Frontiers in Oncology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2024.1338802\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,29]],"date-time":"2024-01-29T04:39:30Z","timestamp":1706503170000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2024.1338802\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,1,29]]},"references-count":59,"alternative-id":["10.3389\/fonc.2024.1338802"],"URL":"https:\/\/doi.org\/10.3389\/fonc.2024.1338802","relation":{},"ISSN":["2234-943X"],"issn-type":[{"value":"2234-943X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,1,29]]},"article-number":"1338802"}}