The Natural Compound Neobractatin Induces Cell Cycle Arrest by Regulating E2F1 and Gadd45α
The complexity and multi-target feature of natural compounds have made it difficult to elucidate their mechanism of action (MoA), which hindered the development of lead anticancer compounds to some extent. In this study, we applied RNA-Seq and GSEA transcriptome analysis to rapidly and efficiently e...
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doaj-3211a4ecb564405db4deb08c2c30c88b2020-11-24T22:01:08ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2019-07-01910.3389/fonc.2019.00654470329The Natural Compound Neobractatin Induces Cell Cycle Arrest by Regulating E2F1 and Gadd45αZhaoqing Zheng0Zhaoqing Zheng1Man Wu2Man Wu3Juan Zhang4Juan Zhang5Wenwei Fu6Wenwei Fu7Naihan Xu8Yuanzhi Lao9Yuanzhi Lao10Lan Lin11Hongxi Xu12Hongxi Xu13School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaEngineering Research Center of Shanghai Colleges for TCM New Drug Discovery, Shanghai, ChinaSchool of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaEngineering Research Center of Shanghai Colleges for TCM New Drug Discovery, Shanghai, ChinaSchool of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaEngineering Research Center of Shanghai Colleges for TCM New Drug Discovery, Shanghai, ChinaSchool of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaEngineering Research Center of Shanghai Colleges for TCM New Drug Discovery, Shanghai, ChinaKey Lab in Health Science and Technology, Division of Life Science, Graduate School at Shenzhen, Tsinghua University, Shenzhen, ChinaSchool of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaEngineering Research Center of Shanghai Colleges for TCM New Drug Discovery, Shanghai, ChinaPerelman School of Medicine, The Children's Hospital of Philadelphia, University of Pennsylvania, Philadelphia, PA, United StatesSchool of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaEngineering Research Center of Shanghai Colleges for TCM New Drug Discovery, Shanghai, ChinaThe complexity and multi-target feature of natural compounds have made it difficult to elucidate their mechanism of action (MoA), which hindered the development of lead anticancer compounds to some extent. In this study, we applied RNA-Seq and GSEA transcriptome analysis to rapidly and efficiently evaluate the anticancer mechanisms of neobractatin (NBT), a caged prenylxanthone isolated from the Chinese herb Garcinia bracteata. We found that NBT exerted anti-proliferative effect on various cancer cells and caused both G1/S and G2/M arrest in synchronized cancer cells through its effects on the expression of E2F1 and GADD45α. The in vivo animal study further suggested that NBT could reduce tumor burden in HeLa xenograft model with no apparent toxicity. By demonstrating the biological effect of NBT, we provided evidences for further investigations of this novel natural compound with anticancer potential.https://www.frontiersin.org/article/10.3389/fonc.2019.00654/fullneobractatincell cycleE2F1GADD45αRNA-SeqGSEA |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Zhaoqing Zheng Zhaoqing Zheng Man Wu Man Wu Juan Zhang Juan Zhang Wenwei Fu Wenwei Fu Naihan Xu Yuanzhi Lao Yuanzhi Lao Lan Lin Hongxi Xu Hongxi Xu |
spellingShingle |
Zhaoqing Zheng Zhaoqing Zheng Man Wu Man Wu Juan Zhang Juan Zhang Wenwei Fu Wenwei Fu Naihan Xu Yuanzhi Lao Yuanzhi Lao Lan Lin Hongxi Xu Hongxi Xu The Natural Compound Neobractatin Induces Cell Cycle Arrest by Regulating E2F1 and Gadd45α Frontiers in Oncology neobractatin cell cycle E2F1 GADD45α RNA-Seq GSEA |
author_facet |
Zhaoqing Zheng Zhaoqing Zheng Man Wu Man Wu Juan Zhang Juan Zhang Wenwei Fu Wenwei Fu Naihan Xu Yuanzhi Lao Yuanzhi Lao Lan Lin Hongxi Xu Hongxi Xu |
author_sort |
Zhaoqing Zheng |
title |
The Natural Compound Neobractatin Induces Cell Cycle Arrest by Regulating E2F1 and Gadd45α |
title_short |
The Natural Compound Neobractatin Induces Cell Cycle Arrest by Regulating E2F1 and Gadd45α |
title_full |
The Natural Compound Neobractatin Induces Cell Cycle Arrest by Regulating E2F1 and Gadd45α |
title_fullStr |
The Natural Compound Neobractatin Induces Cell Cycle Arrest by Regulating E2F1 and Gadd45α |
title_full_unstemmed |
The Natural Compound Neobractatin Induces Cell Cycle Arrest by Regulating E2F1 and Gadd45α |
title_sort |
natural compound neobractatin induces cell cycle arrest by regulating e2f1 and gadd45α |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Oncology |
issn |
2234-943X |
publishDate |
2019-07-01 |
description |
The complexity and multi-target feature of natural compounds have made it difficult to elucidate their mechanism of action (MoA), which hindered the development of lead anticancer compounds to some extent. In this study, we applied RNA-Seq and GSEA transcriptome analysis to rapidly and efficiently evaluate the anticancer mechanisms of neobractatin (NBT), a caged prenylxanthone isolated from the Chinese herb Garcinia bracteata. We found that NBT exerted anti-proliferative effect on various cancer cells and caused both G1/S and G2/M arrest in synchronized cancer cells through its effects on the expression of E2F1 and GADD45α. The in vivo animal study further suggested that NBT could reduce tumor burden in HeLa xenograft model with no apparent toxicity. By demonstrating the biological effect of NBT, we provided evidences for further investigations of this novel natural compound with anticancer potential. |
topic |
neobractatin cell cycle E2F1 GADD45α RNA-Seq GSEA |
url |
https://www.frontiersin.org/article/10.3389/fonc.2019.00654/full |
work_keys_str_mv |
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