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Ultrasound-Activated Microbubble Cancer Therapy: Ceramide Production Leading to Enhanced Radiation Effect in vitro

Blood vessels within tumours represent a key component for cancer cell survival. Disruption of these vessels can be achieved by inducing vascular endothelial-cell apoptosis. Moreover, endothelial cell apoptosis has been proven to be enhanced by ceramide-increasing drugs. Herein, we introduce a novel...

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Autores principales: Nofiele, J. I. T., Karshafian, R., Furukawa, M., Al Mahrouki, A., Giles, A., Wong, S., Czarnota, G. J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: SAGE Publications 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4527482/
https://www.ncbi.nlm.nih.gov/pubmed/22905807
http://dx.doi.org/10.7785/tcrt.2012.500253
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author Nofiele, J. I. T.
Karshafian, R.
Furukawa, M.
Al Mahrouki, A.
Giles, A.
Wong, S.
Czarnota, G. J.
author_facet Nofiele, J. I. T.
Karshafian, R.
Furukawa, M.
Al Mahrouki, A.
Giles, A.
Wong, S.
Czarnota, G. J.
author_sort Nofiele, J. I. T.
collection PubMed
description Blood vessels within tumours represent a key component for cancer cell survival. Disruption of these vessels can be achieved by inducing vascular endothelial-cell apoptosis. Moreover, endothelial cell apoptosis has been proven to be enhanced by ceramide-increasing drugs. Herein, we introduce a novel therapeutic approach which uses ultrasound-stimulated microbubbles used in combination with radiation to cause a rapid accumulation of ceramide in endothelial cells in-vitro. We also test this modality directly with other cell types as a general method of killing cancer cells. Human umbilical vein endothelial cells (HUVEC), acute myeloid leukemia cells (AML), murine fibrosarcoma cells (KHT-C), prostate cancer cells (PC3), breast cancer cells (MDA-MB-231) and astrocytes were used to evaluate this mechanism of inducing cell death. Survival was measured by clonogenic assays, and ceramide content was detected using immunohistochemistry. Exposure of cell types to ultrasound-stimulated bubbles alone resulted in increases in ceramide for all cell types and survivals of 12 ± 2%, 65 ± 5%, 83 ± 2%, 58 ± 4%, 58 ± 3%, 18 ± 7% for HUVEC, AML, PC3, MDA, KHT-C and astrocyte cells, respectively. Results from selected cell types involving radiation treatments indicated additive treatment enhancements and increases in intracellular ceramide content one hour after exposure to ultrasound-activated microbubbles and radiation. Endothelial cell survival decreased from 8 ± 1% after 2 Gy of radiation treatment alone and from 12 ± 2% after ultrasound and microbubbles alone, to 1 ± 1% with combined treatment. In Asmase +/+ astrocytes, survival decreased from 56 ± 2% after 2 Gy radiation alone and from 17 ± 7% after ultrasound and microbubbles alone, to 5 ± 2% when combined. Using ASMase deficient astrocytes (Asmase -/-) and Sphingosine-1-phosphate (S1P), we also demonstrate that ultrasound-activated microbubbles stimulate ASMase activity and ceramide production. These findings suggest that ultrasound-stimulated microbubbles could be used as a new biomechanical method to enhance the effects of radiation.
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spelling pubmed-45274822015-10-07 Ultrasound-Activated Microbubble Cancer Therapy: Ceramide Production Leading to Enhanced Radiation Effect in vitro Nofiele, J. I. T. Karshafian, R. Furukawa, M. Al Mahrouki, A. Giles, A. Wong, S. Czarnota, G. J. Technol Cancer Res Treat Articles Blood vessels within tumours represent a key component for cancer cell survival. Disruption of these vessels can be achieved by inducing vascular endothelial-cell apoptosis. Moreover, endothelial cell apoptosis has been proven to be enhanced by ceramide-increasing drugs. Herein, we introduce a novel therapeutic approach which uses ultrasound-stimulated microbubbles used in combination with radiation to cause a rapid accumulation of ceramide in endothelial cells in-vitro. We also test this modality directly with other cell types as a general method of killing cancer cells. Human umbilical vein endothelial cells (HUVEC), acute myeloid leukemia cells (AML), murine fibrosarcoma cells (KHT-C), prostate cancer cells (PC3), breast cancer cells (MDA-MB-231) and astrocytes were used to evaluate this mechanism of inducing cell death. Survival was measured by clonogenic assays, and ceramide content was detected using immunohistochemistry. Exposure of cell types to ultrasound-stimulated bubbles alone resulted in increases in ceramide for all cell types and survivals of 12 ± 2%, 65 ± 5%, 83 ± 2%, 58 ± 4%, 58 ± 3%, 18 ± 7% for HUVEC, AML, PC3, MDA, KHT-C and astrocyte cells, respectively. Results from selected cell types involving radiation treatments indicated additive treatment enhancements and increases in intracellular ceramide content one hour after exposure to ultrasound-activated microbubbles and radiation. Endothelial cell survival decreased from 8 ± 1% after 2 Gy of radiation treatment alone and from 12 ± 2% after ultrasound and microbubbles alone, to 1 ± 1% with combined treatment. In Asmase +/+ astrocytes, survival decreased from 56 ± 2% after 2 Gy radiation alone and from 17 ± 7% after ultrasound and microbubbles alone, to 5 ± 2% when combined. Using ASMase deficient astrocytes (Asmase -/-) and Sphingosine-1-phosphate (S1P), we also demonstrate that ultrasound-activated microbubbles stimulate ASMase activity and ceramide production. These findings suggest that ultrasound-stimulated microbubbles could be used as a new biomechanical method to enhance the effects of radiation. SAGE Publications 2013-02 /pmc/articles/PMC4527482/ /pubmed/22905807 http://dx.doi.org/10.7785/tcrt.2012.500253 Text en ©Adenine Press (2013)
spellingShingle Articles
Nofiele, J. I. T.
Karshafian, R.
Furukawa, M.
Al Mahrouki, A.
Giles, A.
Wong, S.
Czarnota, G. J.
Ultrasound-Activated Microbubble Cancer Therapy: Ceramide Production Leading to Enhanced Radiation Effect in vitro
title Ultrasound-Activated Microbubble Cancer Therapy: Ceramide Production Leading to Enhanced Radiation Effect in vitro
title_full Ultrasound-Activated Microbubble Cancer Therapy: Ceramide Production Leading to Enhanced Radiation Effect in vitro
title_fullStr Ultrasound-Activated Microbubble Cancer Therapy: Ceramide Production Leading to Enhanced Radiation Effect in vitro
title_full_unstemmed Ultrasound-Activated Microbubble Cancer Therapy: Ceramide Production Leading to Enhanced Radiation Effect in vitro
title_short Ultrasound-Activated Microbubble Cancer Therapy: Ceramide Production Leading to Enhanced Radiation Effect in vitro
title_sort ultrasound-activated microbubble cancer therapy: ceramide production leading to enhanced radiation effect in vitro
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4527482/
https://www.ncbi.nlm.nih.gov/pubmed/22905807
http://dx.doi.org/10.7785/tcrt.2012.500253
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