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(3R)-5,6,7-trihydroxy-3-isopropyl-3-methylisochroman-1-one inhibited osteosarcoma growth by inducing apoptosis

As one of the leading causes of cancer-associated mortalities worldwide, the overall survival rate of osteosarcoma has stably remained at 15–30% for several decades. (3R)- 5,6,7-trihydroxy-3-isopropyl-3-methylisochroman-1-one (TIM), isolated from the whole plant of Selaginella moellendorffii Hieron....

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Detalles Bibliográficos
Autores principales: Song, Ming-Zhu, Zhang, Feng-Lin, Lin, Le-Jun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: D.A. Spandidos 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6601140/
https://www.ncbi.nlm.nih.gov/pubmed/31316606
http://dx.doi.org/10.3892/etm.2019.7681
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author Song, Ming-Zhu
Zhang, Feng-Lin
Lin, Le-Jun
author_facet Song, Ming-Zhu
Zhang, Feng-Lin
Lin, Le-Jun
author_sort Song, Ming-Zhu
collection PubMed
description As one of the leading causes of cancer-associated mortalities worldwide, the overall survival rate of osteosarcoma has stably remained at 15–30% for several decades. (3R)- 5,6,7-trihydroxy-3-isopropyl-3-methylisochroman-1-one (TIM), isolated from the whole plant of Selaginella moellendorffii Hieron., has been reported to have pharmacological activities. In the present study, the anti-proliferative effects of TIM against osteosarcoma were evaluated, and the underlying molecular mechanisms were explored. The results demonstrated that TIM inhibited proliferation and induced apoptosis in U2OS cells. Furthermore, the expression of the pro-apoptotic protein NOXA in the intrinsic apoptosis pathway was upregulated by TIM, while the expression of myeloid cell leukemia 1, an anti-apoptotic protein, was downregulated. In addition, TIM increased the protein expression of the endoplasmic reticulum stress markers inositol-requiring enzyme 1, activating transcription factor 6 and glucose-regulated protein 78. These results suggested that TIM induced ER stress response while activating intrinsic apoptosis. Furthermore, treating osteosarcoma tumor-bearing mice with TIM significantly inhibited the tumor growth in the xenograft animal model. Overall, the study results suggested that TIM may serve as a potential antitumor agent against osteosarcoma.
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spelling pubmed-66011402019-07-17 (3R)-5,6,7-trihydroxy-3-isopropyl-3-methylisochroman-1-one inhibited osteosarcoma growth by inducing apoptosis Song, Ming-Zhu Zhang, Feng-Lin Lin, Le-Jun Exp Ther Med Articles As one of the leading causes of cancer-associated mortalities worldwide, the overall survival rate of osteosarcoma has stably remained at 15–30% for several decades. (3R)- 5,6,7-trihydroxy-3-isopropyl-3-methylisochroman-1-one (TIM), isolated from the whole plant of Selaginella moellendorffii Hieron., has been reported to have pharmacological activities. In the present study, the anti-proliferative effects of TIM against osteosarcoma were evaluated, and the underlying molecular mechanisms were explored. The results demonstrated that TIM inhibited proliferation and induced apoptosis in U2OS cells. Furthermore, the expression of the pro-apoptotic protein NOXA in the intrinsic apoptosis pathway was upregulated by TIM, while the expression of myeloid cell leukemia 1, an anti-apoptotic protein, was downregulated. In addition, TIM increased the protein expression of the endoplasmic reticulum stress markers inositol-requiring enzyme 1, activating transcription factor 6 and glucose-regulated protein 78. These results suggested that TIM induced ER stress response while activating intrinsic apoptosis. Furthermore, treating osteosarcoma tumor-bearing mice with TIM significantly inhibited the tumor growth in the xenograft animal model. Overall, the study results suggested that TIM may serve as a potential antitumor agent against osteosarcoma. D.A. Spandidos 2019-08 2019-06-18 /pmc/articles/PMC6601140/ /pubmed/31316606 http://dx.doi.org/10.3892/etm.2019.7681 Text en Copyright: © Song et al. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
spellingShingle Articles
Song, Ming-Zhu
Zhang, Feng-Lin
Lin, Le-Jun
(3R)-5,6,7-trihydroxy-3-isopropyl-3-methylisochroman-1-one inhibited osteosarcoma growth by inducing apoptosis
title (3R)-5,6,7-trihydroxy-3-isopropyl-3-methylisochroman-1-one inhibited osteosarcoma growth by inducing apoptosis
title_full (3R)-5,6,7-trihydroxy-3-isopropyl-3-methylisochroman-1-one inhibited osteosarcoma growth by inducing apoptosis
title_fullStr (3R)-5,6,7-trihydroxy-3-isopropyl-3-methylisochroman-1-one inhibited osteosarcoma growth by inducing apoptosis
title_full_unstemmed (3R)-5,6,7-trihydroxy-3-isopropyl-3-methylisochroman-1-one inhibited osteosarcoma growth by inducing apoptosis
title_short (3R)-5,6,7-trihydroxy-3-isopropyl-3-methylisochroman-1-one inhibited osteosarcoma growth by inducing apoptosis
title_sort (3r)-5,6,7-trihydroxy-3-isopropyl-3-methylisochroman-1-one inhibited osteosarcoma growth by inducing apoptosis
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6601140/
https://www.ncbi.nlm.nih.gov/pubmed/31316606
http://dx.doi.org/10.3892/etm.2019.7681
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