Exploiting Shock Waves to Trigger the Anticancer Sonodynamic Activity of 5-Aminolevulinc Acid-Derived Protoporphyrin IX on In Vitro 2D and 3D Cancer Models
Sonodynamic therapy (SDT) is a noninvasive method for cancer treatment based on selective activation of a sonosensitiser by ultrasound (US), which results in the generation of reactive oxygen species (ROS) and cancer cell death. SDT uses a similar approach to photodynamic therapy (PDT), but can over...
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MDPI AG
2022-03-01
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author | Federica Foglietta Patrizia Panzanelli Loredana Serpe Roberto Canaparo |
author_facet | Federica Foglietta Patrizia Panzanelli Loredana Serpe Roberto Canaparo |
author_sort | Federica Foglietta |
collection | DOAJ |
description | Sonodynamic therapy (SDT) is a noninvasive method for cancer treatment based on selective activation of a sonosensitiser by ultrasound (US), which results in the generation of reactive oxygen species (ROS) and cancer cell death. SDT uses a similar approach to photodynamic therapy (PDT), but can overcome the main drawback of PDT, i.e., poor tissue penetration of light. This research work investigated the anticancer effect of SDT on various two- (2D) and three-dimensional (3D) in vitro tumour models, using PDT as a reference treatment. Sonodynamic experiments were performed with pulsed US, specifically with shock waves (SW) and the prodrug 5-aminolevulinic acid (Ala), which is converted—at the mitochondrial level—into the sonosensitiser protoporphyrin IX (PPIX). SW-mediated PPIX sonodynamic activation resulted in a significant decrease in cell proliferation, especially on human fibrosarcoma (HT-1080) cells, where PPIX accumulation was higher compared to human melanoma (A2058) and neuroblastoma (SH-SY5 Y) cells. Moreover, SW-mediated SDT showed significant ROS generation, cell line-dependent in its amount, probably due to differences in Ala-induced PPIX synthesis. In all cancer cell lines, apoptosis was highlighted as the main cancer cell death pathway determined by SW-mediated SDT, along with significant cytochrome c release, and a consequent increase in DNA damage. The efficacy of SDT with SW and Ala in halting cancer cell proliferation was also confirmed in 3D cancer spheroids. The present study suggests that SW-mediated SDT is a valuable approach to slow down tumour proliferation, thus opening an innovative scenario in cancer treatment. |
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spelling | doaj.art-3166c47a8cc14817be7210406b5c76882023-11-24T00:32:48ZengMDPI AGBiomedicines2227-90592022-03-0110361510.3390/biomedicines10030615Exploiting Shock Waves to Trigger the Anticancer Sonodynamic Activity of 5-Aminolevulinc Acid-Derived Protoporphyrin IX on In Vitro 2D and 3D Cancer ModelsFederica Foglietta0Patrizia Panzanelli1Loredana Serpe2Roberto Canaparo3Department of Drug Science and Technology, University of Torino, Via Pietro Giuria 13, 10125 Torino, ItalyDepartment of Neuroscience Rita Levi Montalcini, University of Torino, Via Cherasco 15, 10126 Torino, ItalyDepartment of Drug Science and Technology, University of Torino, Via Pietro Giuria 13, 10125 Torino, ItalyDepartment of Drug Science and Technology, University of Torino, Via Pietro Giuria 13, 10125 Torino, ItalySonodynamic therapy (SDT) is a noninvasive method for cancer treatment based on selective activation of a sonosensitiser by ultrasound (US), which results in the generation of reactive oxygen species (ROS) and cancer cell death. SDT uses a similar approach to photodynamic therapy (PDT), but can overcome the main drawback of PDT, i.e., poor tissue penetration of light. This research work investigated the anticancer effect of SDT on various two- (2D) and three-dimensional (3D) in vitro tumour models, using PDT as a reference treatment. Sonodynamic experiments were performed with pulsed US, specifically with shock waves (SW) and the prodrug 5-aminolevulinic acid (Ala), which is converted—at the mitochondrial level—into the sonosensitiser protoporphyrin IX (PPIX). SW-mediated PPIX sonodynamic activation resulted in a significant decrease in cell proliferation, especially on human fibrosarcoma (HT-1080) cells, where PPIX accumulation was higher compared to human melanoma (A2058) and neuroblastoma (SH-SY5 Y) cells. Moreover, SW-mediated SDT showed significant ROS generation, cell line-dependent in its amount, probably due to differences in Ala-induced PPIX synthesis. In all cancer cell lines, apoptosis was highlighted as the main cancer cell death pathway determined by SW-mediated SDT, along with significant cytochrome c release, and a consequent increase in DNA damage. The efficacy of SDT with SW and Ala in halting cancer cell proliferation was also confirmed in 3D cancer spheroids. The present study suggests that SW-mediated SDT is a valuable approach to slow down tumour proliferation, thus opening an innovative scenario in cancer treatment.https://www.mdpi.com/2227-9059/10/3/615shock wavessonodynamic therapy5-aminolevulinc acidprotoporphyrin IXthree-dimensional cancer models |
spellingShingle | Federica Foglietta Patrizia Panzanelli Loredana Serpe Roberto Canaparo Exploiting Shock Waves to Trigger the Anticancer Sonodynamic Activity of 5-Aminolevulinc Acid-Derived Protoporphyrin IX on In Vitro 2D and 3D Cancer Models Biomedicines shock waves sonodynamic therapy 5-aminolevulinc acid protoporphyrin IX three-dimensional cancer models |
title | Exploiting Shock Waves to Trigger the Anticancer Sonodynamic Activity of 5-Aminolevulinc Acid-Derived Protoporphyrin IX on In Vitro 2D and 3D Cancer Models |
title_full | Exploiting Shock Waves to Trigger the Anticancer Sonodynamic Activity of 5-Aminolevulinc Acid-Derived Protoporphyrin IX on In Vitro 2D and 3D Cancer Models |
title_fullStr | Exploiting Shock Waves to Trigger the Anticancer Sonodynamic Activity of 5-Aminolevulinc Acid-Derived Protoporphyrin IX on In Vitro 2D and 3D Cancer Models |
title_full_unstemmed | Exploiting Shock Waves to Trigger the Anticancer Sonodynamic Activity of 5-Aminolevulinc Acid-Derived Protoporphyrin IX on In Vitro 2D and 3D Cancer Models |
title_short | Exploiting Shock Waves to Trigger the Anticancer Sonodynamic Activity of 5-Aminolevulinc Acid-Derived Protoporphyrin IX on In Vitro 2D and 3D Cancer Models |
title_sort | exploiting shock waves to trigger the anticancer sonodynamic activity of 5 aminolevulinc acid derived protoporphyrin ix on in vitro 2d and 3d cancer models |
topic | shock waves sonodynamic therapy 5-aminolevulinc acid protoporphyrin IX three-dimensional cancer models |
url | https://www.mdpi.com/2227-9059/10/3/615 |
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