{"title":"Hemin enhances the 5-aminolevulinic acid-photodynamic therapy effect through the changes of cellular iron homeostasis","authors":"Anantya Pustimbara, Chenhan Li, Shun-ichiro Ogura","doi":"10.1016/j.pdpdt.2024.104253","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><p>Photodynamic therapy (PDT) has been utilized as a promising alternative cancer treatment due to its minimum invasiveness over the years. Exogenous 5-aminolevulinic acid (ALA) triggers protoporphyrin IX (PpIX) accumulation, which happens in cancer cells. However, certain types of cancer exhibit reduced effectiveness in the PpIX accumulation mechanism. This study aimed to determine the effect of ALA-PDT combination with hemin on gastric carcinoma TMK-1 cells.</p></div><div><h3>Methods</h3><p>This study utilized TMK-1 gastric cancer cell line to evaluate PpIX, ROS, and Fe<sup>2+</sup> accumulation following the administration of ALA, hemin, and a combination of ALA and hemin PDT. We also evaluate the mRNA expressions related to iron homeostasis and treatment impacts on cell viability.</p></div><div><h3>Results</h3><p>The co-addition of ALA and hemin PDT for 4 h of treatment resulted in a significant decrease in cell viability by up to 18 %. While ALA-PDT enhanced PpIX metabolism, the addition of hemin influenced both the production of reactive oxygen species (ROS) and cellular iron homeostasis by inducing Fe<sup>2+</sup> accumulation and affecting mRNA levels of <em>IRP, Tfr1, Ferritin, NFS1,</em> and <em>SDHB.</em></p></div><div><h3>Conclusion</h3><p>These findings suggest that the addition of ALA and hemin enhances phototoxicity in TMK-1 cells. The combination of ALA and hemin with PDT induces cell death, evidenced by increased cytotoxicity properties such as PpIX and ROS, along with significant changes in TMK-1 gastric cancer iron homeostasis. Therefore, the combination of ALA and hemin could be one of the alternatives in photodynamic therapy for cancer in the future.</p></div>","PeriodicalId":20141,"journal":{"name":"Photodiagnosis and Photodynamic Therapy","volume":null,"pages":null},"PeriodicalIF":3.1000,"publicationDate":"2024-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1572100024002904/pdfft?md5=a72a80d2b3398fb2d881bd8561b76884&pid=1-s2.0-S1572100024002904-main.pdf","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Photodiagnosis and Photodynamic Therapy","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S1572100024002904","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"ONCOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Background
Photodynamic therapy (PDT) has been utilized as a promising alternative cancer treatment due to its minimum invasiveness over the years. Exogenous 5-aminolevulinic acid (ALA) triggers protoporphyrin IX (PpIX) accumulation, which happens in cancer cells. However, certain types of cancer exhibit reduced effectiveness in the PpIX accumulation mechanism. This study aimed to determine the effect of ALA-PDT combination with hemin on gastric carcinoma TMK-1 cells.
Methods
This study utilized TMK-1 gastric cancer cell line to evaluate PpIX, ROS, and Fe2+ accumulation following the administration of ALA, hemin, and a combination of ALA and hemin PDT. We also evaluate the mRNA expressions related to iron homeostasis and treatment impacts on cell viability.
Results
The co-addition of ALA and hemin PDT for 4 h of treatment resulted in a significant decrease in cell viability by up to 18 %. While ALA-PDT enhanced PpIX metabolism, the addition of hemin influenced both the production of reactive oxygen species (ROS) and cellular iron homeostasis by inducing Fe2+ accumulation and affecting mRNA levels of IRP, Tfr1, Ferritin, NFS1, and SDHB.
Conclusion
These findings suggest that the addition of ALA and hemin enhances phototoxicity in TMK-1 cells. The combination of ALA and hemin with PDT induces cell death, evidenced by increased cytotoxicity properties such as PpIX and ROS, along with significant changes in TMK-1 gastric cancer iron homeostasis. Therefore, the combination of ALA and hemin could be one of the alternatives in photodynamic therapy for cancer in the future.
期刊介绍:
Photodiagnosis and Photodynamic Therapy is an international journal for the dissemination of scientific knowledge and clinical developments of Photodiagnosis and Photodynamic Therapy in all medical specialties. The journal publishes original articles, review articles, case presentations, "how-to-do-it" articles, Letters to the Editor, short communications and relevant images with short descriptions. All submitted material is subject to a strict peer-review process.