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Costunolide Inhibits the Growth of OAW42-A Multidrug-Resistant Human Ovarian Cancer Cells by Activating Apoptotic and Autophagic Pathways, Production of Reactive Oxygen Species (ROS), Cleaved Caspase-3 and Cleaved Caspase-9

BACKGROUND: Worldwide, ovarian cancer has a high mortality rate due to the difficulty in diagnosing early-stage disease and resistance to chemotherapy agents. Costunolide is a plant-derived sesquiterpene lactone with anti-oxidant properties. This study aimed to investigate the effects of costunolide...

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Autores principales: Fang, Yichen, Li, Jie, Wu, Yinan, Gui, Jing, Shen, Yang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: International Scientific Literature, Inc. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6512352/
https://www.ncbi.nlm.nih.gov/pubmed/31043579
http://dx.doi.org/10.12659/MSM.914029
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author Fang, Yichen
Li, Jie
Wu, Yinan
Gui, Jing
Shen, Yang
author_facet Fang, Yichen
Li, Jie
Wu, Yinan
Gui, Jing
Shen, Yang
author_sort Fang, Yichen
collection PubMed
description BACKGROUND: Worldwide, ovarian cancer has a high mortality rate due to the difficulty in diagnosing early-stage disease and resistance to chemotherapy agents. Costunolide is a plant-derived sesquiterpene lactone with anti-oxidant properties. This study aimed to investigate the effects of costunolide on cell growth, apoptosis, autophagy, the production of reactive oxygen species (ROS), cleaved caspase-3, and cleaved caspase-9 on the multidrug-resistant ovarian cancer cell line, OAW42-A. MATERIAL/METHODS: The MTT assay determined the proliferation rate of OAW42-A multidrug-resistant ovarian cancer cells and the apoptosis rate was determined using propidium iodide (PI) staining. Autophagy was detected by measuring the expression of LC3 II. Fluorescence flow cytometry was used to measure the levels of reactive oxygen species (ROS) and the mitochondrial membrane potential. Protein expression of LC3 II, beclin 1, cleaved caspase-3, and cleaved caspase-9 were measured by Western blot. RESULTS: Costunolide treatment inhibited the growth of OAW42-A cells with an IC(50) of 25 μM, resulted in apoptotic cell death, increased the expression of Bax, and decreased the expression of Bcl-2. Confocal electron microscopy showed that costunolide induced autophagy in the OAW42-A cells. Western blot showed that costunolide treatment of OAW42-A cells increased the expression of the LC3 II, beclin 1, cleaved caspase-3, and cleaved caspase-9. Costunolide treatment significantly increased the levels of ROS and reduced the OAW42-A cell mitochondrial membrane potential. CONCLUSIONS: Costunolide inhibited growth, apoptosis, ROS generation, and was associated with loss of mitochondrial membrane potential of OAW42-A multidrug-resistant ovarian cancer cells.
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spelling pubmed-65123522019-06-18 Costunolide Inhibits the Growth of OAW42-A Multidrug-Resistant Human Ovarian Cancer Cells by Activating Apoptotic and Autophagic Pathways, Production of Reactive Oxygen Species (ROS), Cleaved Caspase-3 and Cleaved Caspase-9 Fang, Yichen Li, Jie Wu, Yinan Gui, Jing Shen, Yang Med Sci Monit Lab/In Vitro Research BACKGROUND: Worldwide, ovarian cancer has a high mortality rate due to the difficulty in diagnosing early-stage disease and resistance to chemotherapy agents. Costunolide is a plant-derived sesquiterpene lactone with anti-oxidant properties. This study aimed to investigate the effects of costunolide on cell growth, apoptosis, autophagy, the production of reactive oxygen species (ROS), cleaved caspase-3, and cleaved caspase-9 on the multidrug-resistant ovarian cancer cell line, OAW42-A. MATERIAL/METHODS: The MTT assay determined the proliferation rate of OAW42-A multidrug-resistant ovarian cancer cells and the apoptosis rate was determined using propidium iodide (PI) staining. Autophagy was detected by measuring the expression of LC3 II. Fluorescence flow cytometry was used to measure the levels of reactive oxygen species (ROS) and the mitochondrial membrane potential. Protein expression of LC3 II, beclin 1, cleaved caspase-3, and cleaved caspase-9 were measured by Western blot. RESULTS: Costunolide treatment inhibited the growth of OAW42-A cells with an IC(50) of 25 μM, resulted in apoptotic cell death, increased the expression of Bax, and decreased the expression of Bcl-2. Confocal electron microscopy showed that costunolide induced autophagy in the OAW42-A cells. Western blot showed that costunolide treatment of OAW42-A cells increased the expression of the LC3 II, beclin 1, cleaved caspase-3, and cleaved caspase-9. Costunolide treatment significantly increased the levels of ROS and reduced the OAW42-A cell mitochondrial membrane potential. CONCLUSIONS: Costunolide inhibited growth, apoptosis, ROS generation, and was associated with loss of mitochondrial membrane potential of OAW42-A multidrug-resistant ovarian cancer cells. International Scientific Literature, Inc. 2019-05-02 /pmc/articles/PMC6512352/ /pubmed/31043579 http://dx.doi.org/10.12659/MSM.914029 Text en © Med Sci Monit, 2019 This work is licensed under Creative Common Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0 (https://creativecommons.org/licenses/by-nc-nd/4.0/) )
spellingShingle Lab/In Vitro Research
Fang, Yichen
Li, Jie
Wu, Yinan
Gui, Jing
Shen, Yang
Costunolide Inhibits the Growth of OAW42-A Multidrug-Resistant Human Ovarian Cancer Cells by Activating Apoptotic and Autophagic Pathways, Production of Reactive Oxygen Species (ROS), Cleaved Caspase-3 and Cleaved Caspase-9
title Costunolide Inhibits the Growth of OAW42-A Multidrug-Resistant Human Ovarian Cancer Cells by Activating Apoptotic and Autophagic Pathways, Production of Reactive Oxygen Species (ROS), Cleaved Caspase-3 and Cleaved Caspase-9
title_full Costunolide Inhibits the Growth of OAW42-A Multidrug-Resistant Human Ovarian Cancer Cells by Activating Apoptotic and Autophagic Pathways, Production of Reactive Oxygen Species (ROS), Cleaved Caspase-3 and Cleaved Caspase-9
title_fullStr Costunolide Inhibits the Growth of OAW42-A Multidrug-Resistant Human Ovarian Cancer Cells by Activating Apoptotic and Autophagic Pathways, Production of Reactive Oxygen Species (ROS), Cleaved Caspase-3 and Cleaved Caspase-9
title_full_unstemmed Costunolide Inhibits the Growth of OAW42-A Multidrug-Resistant Human Ovarian Cancer Cells by Activating Apoptotic and Autophagic Pathways, Production of Reactive Oxygen Species (ROS), Cleaved Caspase-3 and Cleaved Caspase-9
title_short Costunolide Inhibits the Growth of OAW42-A Multidrug-Resistant Human Ovarian Cancer Cells by Activating Apoptotic and Autophagic Pathways, Production of Reactive Oxygen Species (ROS), Cleaved Caspase-3 and Cleaved Caspase-9
title_sort costunolide inhibits the growth of oaw42-a multidrug-resistant human ovarian cancer cells by activating apoptotic and autophagic pathways, production of reactive oxygen species (ros), cleaved caspase-3 and cleaved caspase-9
topic Lab/In Vitro Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6512352/
https://www.ncbi.nlm.nih.gov/pubmed/31043579
http://dx.doi.org/10.12659/MSM.914029
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