Radiosensitization by Marine Sponge Agelas sp. Extracts in Hepatocellular Carcinoma Cells with Autophagy Induction

Abstract Although radiation therapy is an effective treatment modality in many cancers, there is an urgent need to develop therapeutic drugs capable of overcoming radioresistance or minimizing normal tissue toxicity. A wide variety of marine-derived bioactive compounds have been screened for anti-ca...

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Main Authors: Changhoon Choi, Arang Son, Hyi-Seung Lee, Yeon-Ju Lee, Hee Chul Park
Format: Article
Language:English
Published: Nature Portfolio 2018-04-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-018-24745-w
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author Changhoon Choi
Arang Son
Hyi-Seung Lee
Yeon-Ju Lee
Hee Chul Park
author_facet Changhoon Choi
Arang Son
Hyi-Seung Lee
Yeon-Ju Lee
Hee Chul Park
author_sort Changhoon Choi
collection DOAJ
description Abstract Although radiation therapy is an effective treatment modality in many cancers, there is an urgent need to develop therapeutic drugs capable of overcoming radioresistance or minimizing normal tissue toxicity. A wide variety of marine-derived bioactive compounds have been screened for anti-cancer drug discovery, but little is known regarding radiation therapy applications. In this study, six different extracts of marine sponges collected from the Micronesian sea were screened for anti-cancer and radiosensitizing activity. Two extracts derived from Agelas sponges collected off the coast of Kosrae and Chuuk, the Federated States of Micronesia significantly decreased clonogenic survival of hepatocellular carcinoma (HCC) cells after exposure to ionizing radiation (IR). The Agelas extracts augmented IR-induced apoptosis and accumulation of reactive oxygen species (ROS). Endoplasmic reticulum (ER) stress was increased via unfolded protein response stimulation, which induced autophagy. N-acetylcysteine, a ROS scavenger, diminished ER stress and autophagy induction effects. This result indicated that Agelas extracts may sensitize HCC cells to IR via ROS overproduction in vitro. Our findings suggest that the Agelas sp. may have potential utility in radiosensitizer development.
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spelling doaj.art-8a53e664818e4e5d930d35f8c76b2f4a2022-12-21T23:37:47ZengNature PortfolioScientific Reports2045-23222018-04-018111010.1038/s41598-018-24745-wRadiosensitization by Marine Sponge Agelas sp. Extracts in Hepatocellular Carcinoma Cells with Autophagy InductionChanghoon Choi0Arang Son1Hyi-Seung Lee2Yeon-Ju Lee3Hee Chul Park4Department of Radiation Oncology, Samsung Medical CenterDepartment of Radiation Oncology, Samsung Medical CenterMarine Natural Product Chemistry Laboratory, Korea Institute of Ocean Science, and TechnologyMarine Natural Product Chemistry Laboratory, Korea Institute of Ocean Science, and TechnologyDepartment of Radiation Oncology, Samsung Medical CenterAbstract Although radiation therapy is an effective treatment modality in many cancers, there is an urgent need to develop therapeutic drugs capable of overcoming radioresistance or minimizing normal tissue toxicity. A wide variety of marine-derived bioactive compounds have been screened for anti-cancer drug discovery, but little is known regarding radiation therapy applications. In this study, six different extracts of marine sponges collected from the Micronesian sea were screened for anti-cancer and radiosensitizing activity. Two extracts derived from Agelas sponges collected off the coast of Kosrae and Chuuk, the Federated States of Micronesia significantly decreased clonogenic survival of hepatocellular carcinoma (HCC) cells after exposure to ionizing radiation (IR). The Agelas extracts augmented IR-induced apoptosis and accumulation of reactive oxygen species (ROS). Endoplasmic reticulum (ER) stress was increased via unfolded protein response stimulation, which induced autophagy. N-acetylcysteine, a ROS scavenger, diminished ER stress and autophagy induction effects. This result indicated that Agelas extracts may sensitize HCC cells to IR via ROS overproduction in vitro. Our findings suggest that the Agelas sp. may have potential utility in radiosensitizer development.https://doi.org/10.1038/s41598-018-24745-w
spellingShingle Changhoon Choi
Arang Son
Hyi-Seung Lee
Yeon-Ju Lee
Hee Chul Park
Radiosensitization by Marine Sponge Agelas sp. Extracts in Hepatocellular Carcinoma Cells with Autophagy Induction
Scientific Reports
title Radiosensitization by Marine Sponge Agelas sp. Extracts in Hepatocellular Carcinoma Cells with Autophagy Induction
title_full Radiosensitization by Marine Sponge Agelas sp. Extracts in Hepatocellular Carcinoma Cells with Autophagy Induction
title_fullStr Radiosensitization by Marine Sponge Agelas sp. Extracts in Hepatocellular Carcinoma Cells with Autophagy Induction
title_full_unstemmed Radiosensitization by Marine Sponge Agelas sp. Extracts in Hepatocellular Carcinoma Cells with Autophagy Induction
title_short Radiosensitization by Marine Sponge Agelas sp. Extracts in Hepatocellular Carcinoma Cells with Autophagy Induction
title_sort radiosensitization by marine sponge agelas sp extracts in hepatocellular carcinoma cells with autophagy induction
url https://doi.org/10.1038/s41598-018-24745-w
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AT hyiseunglee radiosensitizationbymarinespongeagelasspextractsinhepatocellularcarcinomacellswithautophagyinduction
AT yeonjulee radiosensitizationbymarinespongeagelasspextractsinhepatocellularcarcinomacellswithautophagyinduction
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