Purpurogallin is a novel mitogen-activated protein kinase kinase 1/2 inhibitor that suppresses esophageal squamous cell carcinoma growth in vitro and in vivo

Xiaomeng Xie; Xueyin Zu; Feifei Liu; Ting Wang; Xiangyu Wang; Hanyong Chen; Kangdong Liu; Penglei Wang; Fangfang Liu; Yan Zheng; Ann M. Bode; Zigang Dong; Dong Joon Kim

doi:10.1002/mc.23007

Purpurogallin is a novel mitogen-activated protein kinase kinase 1/2 inhibitor that suppresses esophageal squamous cell carcinoma growth in vitro and in vivo

Xiaomeng Xie, Xueyin Zu, Feifei Liu, Ting Wang, Xiangyu Wang, Hanyong Chen, Kangdong Liu, Penglei Wang, Fangfang Liu, Yan Zheng, Ann M. Bode, Zigang Dong, Dong Joon Kim

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21 Scopus citations

Abstract

Purpurogallin is a natural compound that is extracted from nutgalls and oak bark and it possesses antioxidant, anticancer, and anti-inflammatory properties. However, the anticancer capacity of purpurogallin and its molecular target have not been investigated in esophageal squamous cell carcinoma (ESCC). Herein, we report that purpurogallin suppresses ESCC cell growth by directly targeting the mitogen-activated protein kinase kinase 1/2 (MEK1/2) signaling pathway. We found that purpurogallin inhibits anchorage-dependent and -independent ESCC growth. The results of in vitro kinase assays and cell-based assays indicated that purpurogallin also strongly attenuates the extracellular signal-regulated kinase 1/2 (ERK1/2) signaling pathway and also directly binds to and inhibits MEK1 and MEK2 activity. Furthermore, purpurogallin contributed to S and G2 phase cell cycle arrest by reducing cyclin A2 and cyclin B1 expression and also induced apoptosis by activating poly (ADP ribose) polymerase (PARP). Notably, purpurogallin suppressed patient-derived ESCC tumor growth in an in vivo mouse model. These findings indicated that purpurogallin is a novel MEK1/2 inhibitor that could be useful for treating ESCC.

Original language	English (US)
Pages (from-to)	1248-1259
Number of pages	12
Journal	Molecular Carcinogenesis
Volume	58
Issue number	7
DOIs	https://doi.org/10.1002/mc.23007
State	Published - Jan 1 2019

Bibliographical note

Funding Information:
Key program of Henan Province, China, Grant/ Award Number: Grant NO/161100510300; Henan Joint Fund, China, Grant/Award Number: Grant No/U1804196; National Natural Science Foundation China (NSFC), Grant/Award Number: Grant NO/81572812

Funding Information:
This study was supported by Henan Joint Fund, National Natural Science Foundation China (NSFC) (grant numbers U1804196 and 81572812) and Key program of Henan Province, China (grant number 161100510300).

Funding Information:
This study was supported by Henan Joint Fund, National Natural Science Foundation China (NSFC) (grant numbers U1804196 and 81572812) and Key program of Henan Province, China (grant number 161100510300). XX performed the in vitro experiments and assisted with the cell-based and in vivo experiments; FL and XW assisted with the cell-based assays; XZ, TW, YZ, and FL, performed the in vivo experiments; HC performed the computer modeling; KL and AMB supervised the in vivo experimental design, data analysis and manuscript editing; ZD supervised the overall experimental design and data analysis; DJK supervised designed experiments, provided the idea, and prepared the manuscript.

Publisher Copyright:
© 2019 Wiley Periodicals, Inc.

Keywords

esophageal squamous cell carcinoma
mitogen-activated protein kinase kinase
patient-derived xenograft
purpurogallin

PubMed: MeSH publication types

Journal Article
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Xie, X., Zu, X., Liu, F., Wang, T., Wang, X., Chen, H., Liu, K., Wang, P., Liu, F., Zheng, Y., Bode, A. M., Dong, Z., & Kim, D. J. (2019). Purpurogallin is a novel mitogen-activated protein kinase kinase 1/2 inhibitor that suppresses esophageal squamous cell carcinoma growth in vitro and in vivo. Molecular Carcinogenesis, 58(7), 1248-1259. https://doi.org/10.1002/mc.23007

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abstract = "Purpurogallin is a natural compound that is extracted from nutgalls and oak bark and it possesses antioxidant, anticancer, and anti-inflammatory properties. However, the anticancer capacity of purpurogallin and its molecular target have not been investigated in esophageal squamous cell carcinoma (ESCC). Herein, we report that purpurogallin suppresses ESCC cell growth by directly targeting the mitogen-activated protein kinase kinase 1/2 (MEK1/2) signaling pathway. We found that purpurogallin inhibits anchorage-dependent and -independent ESCC growth. The results of in vitro kinase assays and cell-based assays indicated that purpurogallin also strongly attenuates the extracellular signal-regulated kinase 1/2 (ERK1/2) signaling pathway and also directly binds to and inhibits MEK1 and MEK2 activity. Furthermore, purpurogallin contributed to S and G2 phase cell cycle arrest by reducing cyclin A2 and cyclin B1 expression and also induced apoptosis by activating poly (ADP ribose) polymerase (PARP). Notably, purpurogallin suppressed patient-derived ESCC tumor growth in an in vivo mouse model. These findings indicated that purpurogallin is a novel MEK1/2 inhibitor that could be useful for treating ESCC.",

keywords = "esophageal squamous cell carcinoma, mitogen-activated protein kinase kinase, patient-derived xenograft, purpurogallin",

author = "Xiaomeng Xie and Xueyin Zu and Feifei Liu and Ting Wang and Xiangyu Wang and Hanyong Chen and Kangdong Liu and Penglei Wang and Fangfang Liu and Yan Zheng and Bode, {Ann M.} and Zigang Dong and Kim, {Dong Joon}",

note = "Funding Information: Key program of Henan Province, China, Grant/ Award Number: Grant NO/161100510300; Henan Joint Fund, China, Grant/Award Number: Grant No/U1804196; National Natural Science Foundation China (NSFC), Grant/Award Number: Grant NO/81572812 Funding Information: This study was supported by Henan Joint Fund, National Natural Science Foundation China (NSFC) (grant numbers U1804196 and 81572812) and Key program of Henan Province, China (grant number 161100510300). Funding Information: This study was supported by Henan Joint Fund, National Natural Science Foundation China (NSFC) (grant numbers U1804196 and 81572812) and Key program of Henan Province, China (grant number 161100510300). XX performed the in vitro experiments and assisted with the cell-based and in vivo experiments; FL and XW assisted with the cell-based assays; XZ, TW, YZ, and FL, performed the in vivo experiments; HC performed the computer modeling; KL and AMB supervised the in vivo experimental design, data analysis and manuscript editing; ZD supervised the overall experimental design and data analysis; DJK supervised designed experiments, provided the idea, and prepared the manuscript. Publisher Copyright: {\textcopyright} 2019 Wiley Periodicals, Inc.",

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AU - Xie, Xiaomeng

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AU - Liu, Feifei

AU - Wang, Ting

AU - Wang, Xiangyu

AU - Chen, Hanyong

AU - Liu, Kangdong

AU - Wang, Penglei

AU - Liu, Fangfang

AU - Zheng, Yan

AU - Bode, Ann M.

AU - Dong, Zigang

AU - Kim, Dong Joon

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N2 - Purpurogallin is a natural compound that is extracted from nutgalls and oak bark and it possesses antioxidant, anticancer, and anti-inflammatory properties. However, the anticancer capacity of purpurogallin and its molecular target have not been investigated in esophageal squamous cell carcinoma (ESCC). Herein, we report that purpurogallin suppresses ESCC cell growth by directly targeting the mitogen-activated protein kinase kinase 1/2 (MEK1/2) signaling pathway. We found that purpurogallin inhibits anchorage-dependent and -independent ESCC growth. The results of in vitro kinase assays and cell-based assays indicated that purpurogallin also strongly attenuates the extracellular signal-regulated kinase 1/2 (ERK1/2) signaling pathway and also directly binds to and inhibits MEK1 and MEK2 activity. Furthermore, purpurogallin contributed to S and G2 phase cell cycle arrest by reducing cyclin A2 and cyclin B1 expression and also induced apoptosis by activating poly (ADP ribose) polymerase (PARP). Notably, purpurogallin suppressed patient-derived ESCC tumor growth in an in vivo mouse model. These findings indicated that purpurogallin is a novel MEK1/2 inhibitor that could be useful for treating ESCC.

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Purpurogallin is a novel mitogen-activated protein kinase kinase 1/2 inhibitor that suppresses esophageal squamous cell carcinoma growth in vitro and in vivo

Abstract

Bibliographical note

Keywords

PubMed: MeSH publication types

UN SDGs

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