4-Methylumbelliferone administration enhances radiosensitivity of human fibrosarcoma by intercellular communication

Abstract Hyaluronan synthesis inhibitor 4-methylumbelliferone (4-MU) is a candidate of radiosensitizers which enables both anti-tumour and anti-metastasis effects in X-ray therapy. The curative effects under such 4-MU administration have been investigated in vitro; however, the radiosensitizing mech...

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Autores principales:	Ryo Saga, Yusuke Matsuya, Rei Takahashi, Kazuki Hasegawa, Hiroyuki Date, Yoichiro Hosokawa
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/70e6ccd9f13047efa76fb91d40b2720f
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spelling	oai:doaj.org-article:70e6ccd9f13047efa76fb91d40b2720f2021-12-02T14:26:20Z4-Methylumbelliferone administration enhances radiosensitivity of human fibrosarcoma by intercellular communication10.1038/s41598-021-87850-32045-2322https://doaj.org/article/70e6ccd9f13047efa76fb91d40b2720f2021-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-87850-3https://doaj.org/toc/2045-2322Abstract Hyaluronan synthesis inhibitor 4-methylumbelliferone (4-MU) is a candidate of radiosensitizers which enables both anti-tumour and anti-metastasis effects in X-ray therapy. The curative effects under such 4-MU administration have been investigated in vitro; however, the radiosensitizing mechanisms remain unclear. Here, we investigated the radiosensitizing effects under 4-MU treatment from cell experiments and model estimations. We generated experimental surviving fractions of human fibrosarcoma cells (HT1080) after 4-MU treatment combined with X-ray irradiation. Meanwhilst, we also modelled the pharmacological effects of 4-MU treatment and theoretically analyzed the synergetic effects between 4-MU treatment and X-ray irradiation. The results show that the enhancement of cell killing by 4-MU treatment is the greatest in the intermediate dose range of around 4 Gy, which can be reproduced by considering intercellular communication (so called non-targeted effects) through the model analysis. As supposed to be the involvement of intercellular communication in radiosensitization, the oxidative stress level associated with reactive oxygen species (ROS), which leads to DNA damage induction, is significantly higher by the combination of 4-MU treatment and irradiation than only by X-ray irradiation, and the radiosensitization by 4-MU can be suppressed by the ROS inhibitors. These findings suggest that the synergetic effects between 4-MU treatment and irradiation are predominantly attributed to intercellular communication and provide more efficient tumour control than conventional X-ray therapy.Ryo SagaYusuke MatsuyaRei TakahashiKazuki HasegawaHiroyuki DateYoichiro HosokawaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Ryo Saga Yusuke Matsuya Rei Takahashi Kazuki Hasegawa Hiroyuki Date Yoichiro Hosokawa 4-Methylumbelliferone administration enhances radiosensitivity of human fibrosarcoma by intercellular communication
description	Abstract Hyaluronan synthesis inhibitor 4-methylumbelliferone (4-MU) is a candidate of radiosensitizers which enables both anti-tumour and anti-metastasis effects in X-ray therapy. The curative effects under such 4-MU administration have been investigated in vitro; however, the radiosensitizing mechanisms remain unclear. Here, we investigated the radiosensitizing effects under 4-MU treatment from cell experiments and model estimations. We generated experimental surviving fractions of human fibrosarcoma cells (HT1080) after 4-MU treatment combined with X-ray irradiation. Meanwhilst, we also modelled the pharmacological effects of 4-MU treatment and theoretically analyzed the synergetic effects between 4-MU treatment and X-ray irradiation. The results show that the enhancement of cell killing by 4-MU treatment is the greatest in the intermediate dose range of around 4 Gy, which can be reproduced by considering intercellular communication (so called non-targeted effects) through the model analysis. As supposed to be the involvement of intercellular communication in radiosensitization, the oxidative stress level associated with reactive oxygen species (ROS), which leads to DNA damage induction, is significantly higher by the combination of 4-MU treatment and irradiation than only by X-ray irradiation, and the radiosensitization by 4-MU can be suppressed by the ROS inhibitors. These findings suggest that the synergetic effects between 4-MU treatment and irradiation are predominantly attributed to intercellular communication and provide more efficient tumour control than conventional X-ray therapy.
format	article
author	Ryo Saga Yusuke Matsuya Rei Takahashi Kazuki Hasegawa Hiroyuki Date Yoichiro Hosokawa
author_facet	Ryo Saga Yusuke Matsuya Rei Takahashi Kazuki Hasegawa Hiroyuki Date Yoichiro Hosokawa
author_sort	Ryo Saga
title	4-Methylumbelliferone administration enhances radiosensitivity of human fibrosarcoma by intercellular communication
title_short	4-Methylumbelliferone administration enhances radiosensitivity of human fibrosarcoma by intercellular communication
title_full	4-Methylumbelliferone administration enhances radiosensitivity of human fibrosarcoma by intercellular communication
title_fullStr	4-Methylumbelliferone administration enhances radiosensitivity of human fibrosarcoma by intercellular communication
title_full_unstemmed	4-Methylumbelliferone administration enhances radiosensitivity of human fibrosarcoma by intercellular communication
title_sort	4-methylumbelliferone administration enhances radiosensitivity of human fibrosarcoma by intercellular communication
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/70e6ccd9f13047efa76fb91d40b2720f
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4-Methylumbelliferone administration enhances radiosensitivity of human fibrosarcoma by intercellular communication

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