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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Main Authors: Zhaoqing Zheng, Man Wu, Juan Zhang, Wenwei Fu, Naihan Xu, Yuanzhi Lao, Lan Lin, Hongxi Xu
Format: Article
Language:English
Published: Frontiers Media S.A. 2019-07-01
Series:Frontiers in Oncology
Subjects:
Online Access:https://www.frontiersin.org/article/10.3389/fonc.2019.00654/full
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spelling 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
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