Cancer stem cell populations are resistant to 5-aminolevulinic acid-photodynamic therapy (5-ALA-PDT)
Abstract Photodynamic therapy (PDT) is a minimally invasive treatment approved for many types of cancers. PDT involves the administration of photoactive substances called photosensitizers (PS) that selectively accumulate in cancer cells and are subsequently excited/activated by irradiation with ligh...
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Nature Portfolio
2025-02-01
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| Online Access: | https://doi.org/10.1038/s41598-025-88173-3 |
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| author | Chantel P. J. Rice Vipin Shankar Chelakkot Noah T. Conohan Kensuke Hirasawa |
| author_facet | Chantel P. J. Rice Vipin Shankar Chelakkot Noah T. Conohan Kensuke Hirasawa |
| author_sort | Chantel P. J. Rice |
| collection | DOAJ |
| description | Abstract Photodynamic therapy (PDT) is a minimally invasive treatment approved for many types of cancers. PDT involves the administration of photoactive substances called photosensitizers (PS) that selectively accumulate in cancer cells and are subsequently excited/activated by irradiation with light at wavelengths of optimal absorbance. Activated PS leads to the generation of singlet oxygen and other reactive oxygen species (ROS), promoting cancer cell death. 5-aminolevulinic acid (5-ALA) is a naturally occurring PS precursor, which is metabolically converted to the PS, protoporphyrin IX (PPIX). Although 5-ALA-PDT is effective at killing cancer cells, in prior studies conducted by our group we normally observed in in vitro experiments that approximately 5–10% of cells survive 5-ALA-PDT, which served as an impetus for further investigation. Identifying the mechanisms of resistance to 5-ALA-PDT-mediated cell death is important to prevent tumor recurrence following 5-ALA-PDT. Previously, we reported that oncogenic activation of Ras/MEK promotes PPIX efflux and reduces cellular sensitivity to 5-ALA-PDT through increased expression of ABCB1 transporter. As cancer stem cells (CSCs) are known to drive resistance to other cancer treatments and have high efflux of chemotherapeutic agents via ABC-family transporters, we hypothesize that CSCs underlie 5-ALA-PDT resistance. In this study, we determined (1) if CSCs are resistant to 5-ALA-PDT and (2) if CSCs play roles in establishing resistant populations of 5-ALA-PDT. When we compared CSC populations before and after 5-ALA-PDT, we found that CSCs were less susceptible to 5-ALA-PDT. Moreover, we found that the CSC population was enriched in 5-ALA-PDT-resistant cell lines compared to the parental cell line. Our results indicate that CSCs are not sensitive to 5-ALA-PDT, which may contribute to establishment of 5-ALA-PDT resistance. |
| format | Article |
| id | doaj-art-e575c89b696544f1a6a02a1b167f189f |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Nature Portfolio |
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| series | Scientific Reports |
| spelling | doaj-art-e575c89b696544f1a6a02a1b167f189f2025-02-09T12:35:54ZengNature PortfolioScientific Reports2045-23222025-02-011511910.1038/s41598-025-88173-3Cancer stem cell populations are resistant to 5-aminolevulinic acid-photodynamic therapy (5-ALA-PDT)Chantel P. J. Rice0Vipin Shankar Chelakkot1Noah T. Conohan2Kensuke Hirasawa3Division of BioMedical Sciences, Memorial University of NewfoundlandDivision of BioMedical Sciences, Memorial University of NewfoundlandDivision of BioMedical Sciences, Memorial University of NewfoundlandDivision of BioMedical Sciences, Memorial University of NewfoundlandAbstract Photodynamic therapy (PDT) is a minimally invasive treatment approved for many types of cancers. PDT involves the administration of photoactive substances called photosensitizers (PS) that selectively accumulate in cancer cells and are subsequently excited/activated by irradiation with light at wavelengths of optimal absorbance. Activated PS leads to the generation of singlet oxygen and other reactive oxygen species (ROS), promoting cancer cell death. 5-aminolevulinic acid (5-ALA) is a naturally occurring PS precursor, which is metabolically converted to the PS, protoporphyrin IX (PPIX). Although 5-ALA-PDT is effective at killing cancer cells, in prior studies conducted by our group we normally observed in in vitro experiments that approximately 5–10% of cells survive 5-ALA-PDT, which served as an impetus for further investigation. Identifying the mechanisms of resistance to 5-ALA-PDT-mediated cell death is important to prevent tumor recurrence following 5-ALA-PDT. Previously, we reported that oncogenic activation of Ras/MEK promotes PPIX efflux and reduces cellular sensitivity to 5-ALA-PDT through increased expression of ABCB1 transporter. As cancer stem cells (CSCs) are known to drive resistance to other cancer treatments and have high efflux of chemotherapeutic agents via ABC-family transporters, we hypothesize that CSCs underlie 5-ALA-PDT resistance. In this study, we determined (1) if CSCs are resistant to 5-ALA-PDT and (2) if CSCs play roles in establishing resistant populations of 5-ALA-PDT. When we compared CSC populations before and after 5-ALA-PDT, we found that CSCs were less susceptible to 5-ALA-PDT. Moreover, we found that the CSC population was enriched in 5-ALA-PDT-resistant cell lines compared to the parental cell line. Our results indicate that CSCs are not sensitive to 5-ALA-PDT, which may contribute to establishment of 5-ALA-PDT resistance.https://doi.org/10.1038/s41598-025-88173-35-aminolevulinic acid (5-ALA)Photodynamic therapy (PDT)Cancer stem cells (CSCs)CD1335-ALA-PDT resistance |
| spellingShingle | Chantel P. J. Rice Vipin Shankar Chelakkot Noah T. Conohan Kensuke Hirasawa Cancer stem cell populations are resistant to 5-aminolevulinic acid-photodynamic therapy (5-ALA-PDT) Scientific Reports 5-aminolevulinic acid (5-ALA) Photodynamic therapy (PDT) Cancer stem cells (CSCs) CD133 5-ALA-PDT resistance |
| title | Cancer stem cell populations are resistant to 5-aminolevulinic acid-photodynamic therapy (5-ALA-PDT) |
| title_full | Cancer stem cell populations are resistant to 5-aminolevulinic acid-photodynamic therapy (5-ALA-PDT) |
| title_fullStr | Cancer stem cell populations are resistant to 5-aminolevulinic acid-photodynamic therapy (5-ALA-PDT) |
| title_full_unstemmed | Cancer stem cell populations are resistant to 5-aminolevulinic acid-photodynamic therapy (5-ALA-PDT) |
| title_short | Cancer stem cell populations are resistant to 5-aminolevulinic acid-photodynamic therapy (5-ALA-PDT) |
| title_sort | cancer stem cell populations are resistant to 5 aminolevulinic acid photodynamic therapy 5 ala pdt |
| topic | 5-aminolevulinic acid (5-ALA) Photodynamic therapy (PDT) Cancer stem cells (CSCs) CD133 5-ALA-PDT resistance |
| url | https://doi.org/10.1038/s41598-025-88173-3 |
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