Red Light and 5% Aminolaevulinic Acid (5%) Inhibit Proliferation and Migration of Dysplastic Oral Keratinocytes via ROS Production: An In Vitro Study
Undiagnosed and untreated oral precancerous lesions often progress into malignancies. Photodynamic therapy (PDT) might be a minimally invasive alternative to conventional treatments. 5-aminolevulinic acid (5-ALA) is one of the most commonly used photosensitizers in PDT, and it is effective on many c...
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MDPI AG
2023-07-01
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| author | Tania Vanessa Pierfelice Milos Lazarevic Dijana Mitic Nadja Nikolic Milena Radunovic Giovanna Iezzi Adriano Piattelli Jelena Milasin |
| author_facet | Tania Vanessa Pierfelice Milos Lazarevic Dijana Mitic Nadja Nikolic Milena Radunovic Giovanna Iezzi Adriano Piattelli Jelena Milasin |
| author_sort | Tania Vanessa Pierfelice |
| collection | DOAJ |
| description | Undiagnosed and untreated oral precancerous lesions often progress into malignancies. Photodynamic therapy (PDT) might be a minimally invasive alternative to conventional treatments. 5-aminolevulinic acid (5-ALA) is one of the most commonly used photosensitizers in PDT, and it is effective on many cancer types. However, its hydrophilic characteristic limits cell membrane crossing. In the present study, the effect of a newly formulated gel containing 5% 5-ALA in combination with red light (ALAD-PDT) on a premalignant oral mucosa cell line was investigated. The dysplastic oral keratinocyte (DOK) cells were incubated with ALAD at different concentrations (0.1, 0.5, 1, and 2 mM) at two different times, 45 min or 4 h, and then irradiated for 7 min with a 630 nm LED (25 J/cm<sup>2</sup>). MTT assay, flow cytometry, wound healing assay, and quantitative PCR (qPCR) were performed. ALAD-PDT exerted inhibitory effects on the proliferation and migration of DOK cells by inducing ROS and necrosis. mRNA analysis showed modulation of apoptosis-related genes’ expression (TP53, Bcl-2, survivin, caspase-3, and caspase-9). Furthermore, there was no difference between the shorter and longer incubation times. In conclusion, the inhibitory effect of the ALAD-PDT protocol observed in this study suggests that ALAD-PDT could be a promising novel treatment for oral precancerous lesions. |
| first_indexed | 2024-03-10T23:55:06Z |
| format | Article |
| id | doaj.art-37ae97a7b77b44729d5593ae9484ab0a |
| institution | Directory Open Access Journal |
| issn | 2310-2861 |
| language | English |
| last_indexed | 2024-03-10T23:55:06Z |
| publishDate | 2023-07-01 |
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| series | Gels |
| spelling | doaj.art-37ae97a7b77b44729d5593ae9484ab0a2023-11-19T01:13:04ZengMDPI AGGels2310-28612023-07-019860410.3390/gels9080604Red Light and 5% Aminolaevulinic Acid (5%) Inhibit Proliferation and Migration of Dysplastic Oral Keratinocytes via ROS Production: An In Vitro StudyTania Vanessa Pierfelice0Milos Lazarevic1Dijana Mitic2Nadja Nikolic3Milena Radunovic4Giovanna Iezzi5Adriano Piattelli6Jelena Milasin7Department of Medical, Oral and Biotechnological Sciences, University G. d’Annunzio of Chieti-Pescara, 66100 Chieti, ItalyDepartment of Human Genetics, School of Dental Medicine, University of Belgrade, Dr Subotica 8, 11000 Belgrade, SerbiaDepartment of Human Genetics, School of Dental Medicine, University of Belgrade, Dr Subotica 8, 11000 Belgrade, SerbiaDepartment of Human Genetics, School of Dental Medicine, University of Belgrade, Dr Subotica 8, 11000 Belgrade, SerbiaDepartment of Microbiology and Immunology, School of Dental Medicine, University of Belgrade, Dr Subotica 8, 11000 Belgrade, SerbiaDepartment of Medical, Oral and Biotechnological Sciences, University G. d’Annunzio of Chieti-Pescara, 66100 Chieti, ItalySchool of Dentistry, Saint Camillus International University of Health and Medical Sciences, 00131 Rome, ItalyDepartment of Human Genetics, School of Dental Medicine, University of Belgrade, Dr Subotica 8, 11000 Belgrade, SerbiaUndiagnosed and untreated oral precancerous lesions often progress into malignancies. Photodynamic therapy (PDT) might be a minimally invasive alternative to conventional treatments. 5-aminolevulinic acid (5-ALA) is one of the most commonly used photosensitizers in PDT, and it is effective on many cancer types. However, its hydrophilic characteristic limits cell membrane crossing. In the present study, the effect of a newly formulated gel containing 5% 5-ALA in combination with red light (ALAD-PDT) on a premalignant oral mucosa cell line was investigated. The dysplastic oral keratinocyte (DOK) cells were incubated with ALAD at different concentrations (0.1, 0.5, 1, and 2 mM) at two different times, 45 min or 4 h, and then irradiated for 7 min with a 630 nm LED (25 J/cm<sup>2</sup>). MTT assay, flow cytometry, wound healing assay, and quantitative PCR (qPCR) were performed. ALAD-PDT exerted inhibitory effects on the proliferation and migration of DOK cells by inducing ROS and necrosis. mRNA analysis showed modulation of apoptosis-related genes’ expression (TP53, Bcl-2, survivin, caspase-3, and caspase-9). Furthermore, there was no difference between the shorter and longer incubation times. In conclusion, the inhibitory effect of the ALAD-PDT protocol observed in this study suggests that ALAD-PDT could be a promising novel treatment for oral precancerous lesions.https://www.mdpi.com/2310-2861/9/8/6045-ALALEDphotodynamic therapydysplastic oral keratinocytes (DOK)ROSnecrosis |
| spellingShingle | Tania Vanessa Pierfelice Milos Lazarevic Dijana Mitic Nadja Nikolic Milena Radunovic Giovanna Iezzi Adriano Piattelli Jelena Milasin Red Light and 5% Aminolaevulinic Acid (5%) Inhibit Proliferation and Migration of Dysplastic Oral Keratinocytes via ROS Production: An In Vitro Study Gels 5-ALA LED photodynamic therapy dysplastic oral keratinocytes (DOK) ROS necrosis |
| title | Red Light and 5% Aminolaevulinic Acid (5%) Inhibit Proliferation and Migration of Dysplastic Oral Keratinocytes via ROS Production: An In Vitro Study |
| title_full | Red Light and 5% Aminolaevulinic Acid (5%) Inhibit Proliferation and Migration of Dysplastic Oral Keratinocytes via ROS Production: An In Vitro Study |
| title_fullStr | Red Light and 5% Aminolaevulinic Acid (5%) Inhibit Proliferation and Migration of Dysplastic Oral Keratinocytes via ROS Production: An In Vitro Study |
| title_full_unstemmed | Red Light and 5% Aminolaevulinic Acid (5%) Inhibit Proliferation and Migration of Dysplastic Oral Keratinocytes via ROS Production: An In Vitro Study |
| title_short | Red Light and 5% Aminolaevulinic Acid (5%) Inhibit Proliferation and Migration of Dysplastic Oral Keratinocytes via ROS Production: An In Vitro Study |
| title_sort | red light and 5 aminolaevulinic acid 5 inhibit proliferation and migration of dysplastic oral keratinocytes via ros production an in vitro study |
| topic | 5-ALA LED photodynamic therapy dysplastic oral keratinocytes (DOK) ROS necrosis |
| url | https://www.mdpi.com/2310-2861/9/8/604 |
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