An Efficient 5-Aminolevulinic Acid Photodynamic Therapy Treatment for Human Hepatocellular Carcinoma
Photodynamic therapy (PDT) is a two-stage treatment relying on cytotoxicity induced by photoexcitation of a nontoxic dye, called photosensitizer (PS). Using 5-aminolevulinic acid (5-ALA), the pro-drug of PS protoporphyrin IX, we investigated the impact of PDT on hepatocellular carcinoma (HCC). Optim...
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| Language: | English |
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MDPI AG
2023-06-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/13/10426 |
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| author | Abhishek Kumar Florian Pecquenard Martha Baydoun Alexandre Quilbé Olivier Moralès Bertrand Leroux Lynda Aoudjehane Filomena Conti Emmanuel Boleslawski Nadira Delhem |
| author_facet | Abhishek Kumar Florian Pecquenard Martha Baydoun Alexandre Quilbé Olivier Moralès Bertrand Leroux Lynda Aoudjehane Filomena Conti Emmanuel Boleslawski Nadira Delhem |
| author_sort | Abhishek Kumar |
| collection | DOAJ |
| description | Photodynamic therapy (PDT) is a two-stage treatment relying on cytotoxicity induced by photoexcitation of a nontoxic dye, called photosensitizer (PS). Using 5-aminolevulinic acid (5-ALA), the pro-drug of PS protoporphyrin IX, we investigated the impact of PDT on hepatocellular carcinoma (HCC). Optimal 5-ALA PDT dose was determined on three HCC cell lines by analyzing cell death after treatment with varying doses. HCC-patient-derived tumor hepatocytes and healthy donor liver myofibroblasts were treated with optimal 5-ALA PDT doses. The proliferation of cancer cells and healthy donor immune cells cultured with 5-ALA-PDT-treated conditioned media was analyzed. Finally, therapy efficacy on humanized SCID mice model of HCC was investigated. 5-ALA PDT induced a dose-dependent decrease in viability, with an up-to-four-fold reduction in viability of patient tumor hepatocytes. The 5-ALA PDT treated conditioned media induced immune cell clonal expansion. 5-ALA PDT has no impact on myofibroblasts in terms of viability, while their activation decreased cancer cell proliferation and reduced the tumor growth rate of the in vivo model. For the first time, 5-ALA PDT has been validated on primary patient tumor hepatocytes and donor healthy liver myofibroblasts. 5-ALA PDT may be an effective anti-HCC therapy, which might induce an anti-tumor immune response. |
| first_indexed | 2024-03-11T01:40:29Z |
| format | Article |
| id | doaj.art-e1c9b49f77194fc2af4a8c6f0447bb41 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T01:40:29Z |
| publishDate | 2023-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-e1c9b49f77194fc2af4a8c6f0447bb412023-11-18T16:37:59ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-06-0124131042610.3390/ijms241310426An Efficient 5-Aminolevulinic Acid Photodynamic Therapy Treatment for Human Hepatocellular CarcinomaAbhishek Kumar0Florian Pecquenard1Martha Baydoun2Alexandre Quilbé3Olivier Moralès4Bertrand Leroux5Lynda Aoudjehane6Filomena Conti7Emmanuel Boleslawski8Nadira Delhem9Univ. Lille, Inserm, CHU Lille, U1189-ONCO-THAI-Assisted Laser Therapy and Immunotherapy for Oncology, F-59000 Lille, FranceUniv. Lille, Inserm, CHU Lille, U1189-ONCO-THAI-Assisted Laser Therapy and Immunotherapy for Oncology, F-59000 Lille, FranceUniv. Lille, Inserm, CHU Lille, U1189-ONCO-THAI-Assisted Laser Therapy and Immunotherapy for Oncology, F-59000 Lille, FranceUniv. Lille, Inserm, CHU Lille, U1189-ONCO-THAI-Assisted Laser Therapy and Immunotherapy for Oncology, F-59000 Lille, FranceUniv. Lille, Inserm, CHU Lille, U1189-ONCO-THAI-Assisted Laser Therapy and Immunotherapy for Oncology, F-59000 Lille, FranceUniv. Lille, Inserm, CHU Lille, U1189-ONCO-THAI-Assisted Laser Therapy and Immunotherapy for Oncology, F-59000 Lille, FranceINSERM, Institute of Cardiometabolism and Nutrition (ICAN), Sorbonne Université, F-75013 Paris, FranceINSERM, Institute of Cardiometabolism and Nutrition (ICAN), Sorbonne Université, F-75013 Paris, FranceUniv. Lille, Inserm, CHU Lille, U1189-ONCO-THAI-Assisted Laser Therapy and Immunotherapy for Oncology, F-59000 Lille, FranceUniv. Lille, Inserm, CHU Lille, U1189-ONCO-THAI-Assisted Laser Therapy and Immunotherapy for Oncology, F-59000 Lille, FrancePhotodynamic therapy (PDT) is a two-stage treatment relying on cytotoxicity induced by photoexcitation of a nontoxic dye, called photosensitizer (PS). Using 5-aminolevulinic acid (5-ALA), the pro-drug of PS protoporphyrin IX, we investigated the impact of PDT on hepatocellular carcinoma (HCC). Optimal 5-ALA PDT dose was determined on three HCC cell lines by analyzing cell death after treatment with varying doses. HCC-patient-derived tumor hepatocytes and healthy donor liver myofibroblasts were treated with optimal 5-ALA PDT doses. The proliferation of cancer cells and healthy donor immune cells cultured with 5-ALA-PDT-treated conditioned media was analyzed. Finally, therapy efficacy on humanized SCID mice model of HCC was investigated. 5-ALA PDT induced a dose-dependent decrease in viability, with an up-to-four-fold reduction in viability of patient tumor hepatocytes. The 5-ALA PDT treated conditioned media induced immune cell clonal expansion. 5-ALA PDT has no impact on myofibroblasts in terms of viability, while their activation decreased cancer cell proliferation and reduced the tumor growth rate of the in vivo model. For the first time, 5-ALA PDT has been validated on primary patient tumor hepatocytes and donor healthy liver myofibroblasts. 5-ALA PDT may be an effective anti-HCC therapy, which might induce an anti-tumor immune response.https://www.mdpi.com/1422-0067/24/13/10426photodynamic therapyhepatocellular carcinoma5-ALAanti-tumor immunotherapyanti-tumor immunity |
| spellingShingle | Abhishek Kumar Florian Pecquenard Martha Baydoun Alexandre Quilbé Olivier Moralès Bertrand Leroux Lynda Aoudjehane Filomena Conti Emmanuel Boleslawski Nadira Delhem An Efficient 5-Aminolevulinic Acid Photodynamic Therapy Treatment for Human Hepatocellular Carcinoma International Journal of Molecular Sciences photodynamic therapy hepatocellular carcinoma 5-ALA anti-tumor immunotherapy anti-tumor immunity |
| title | An Efficient 5-Aminolevulinic Acid Photodynamic Therapy Treatment for Human Hepatocellular Carcinoma |
| title_full | An Efficient 5-Aminolevulinic Acid Photodynamic Therapy Treatment for Human Hepatocellular Carcinoma |
| title_fullStr | An Efficient 5-Aminolevulinic Acid Photodynamic Therapy Treatment for Human Hepatocellular Carcinoma |
| title_full_unstemmed | An Efficient 5-Aminolevulinic Acid Photodynamic Therapy Treatment for Human Hepatocellular Carcinoma |
| title_short | An Efficient 5-Aminolevulinic Acid Photodynamic Therapy Treatment for Human Hepatocellular Carcinoma |
| title_sort | efficient 5 aminolevulinic acid photodynamic therapy treatment for human hepatocellular carcinoma |
| topic | photodynamic therapy hepatocellular carcinoma 5-ALA anti-tumor immunotherapy anti-tumor immunity |
| url | https://www.mdpi.com/1422-0067/24/13/10426 |
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