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

Research output: Contribution to journalArticle

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 languageEnglish (US)
Pages (from-to)1248-1259
Number of pages12
JournalMolecular Carcinogenesis
Volume58
Issue number7
DOIs
StatePublished - Jan 1 2019

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MAP Kinase Kinase 2
MAP Kinase Kinase 1
Growth
Cyclin A2
G2 Phase Cell Cycle Checkpoints
Cyclin B1
Mitogen-Activated Protein Kinase 3
Poly(ADP-ribose) Polymerases
Esophageal Squamous Cell Carcinoma
purpurogallin
In Vitro Techniques
G2 Phase
Mitogen-Activated Protein Kinase 1
S Phase
Anti-Inflammatory Agents
Phosphotransferases
Antioxidants
Apoptosis

Keywords

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

PubMed: MeSH publication types

  • Journal Article

Cite this

Purpurogallin is a novel mitogen-activated protein kinase kinase 1/2 inhibitor that suppresses esophageal squamous cell carcinoma growth in vitro and in vivo. / Xie, Xiaomeng; Zu, Xueyin; Liu, Feifei; Wang, Ting; Wang, Xiangyu; Chen, Hanyong; Liu, Kangdong; Wang, Penglei; Liu, Fangfang; Zheng, Yan; Bode, Ann M.; Dong, Zigang; Kim, Dong Joon.

In: Molecular Carcinogenesis, Vol. 58, No. 7, 01.01.2019, p. 1248-1259.

Research output: Contribution to journalArticle

Xie, Xiaomeng ; Zu, Xueyin ; Liu, Feifei ; Wang, Ting ; Wang, Xiangyu ; Chen, Hanyong ; Liu, Kangdong ; Wang, Penglei ; Liu, Fangfang ; Zheng, Yan ; Bode, Ann M. ; Dong, Zigang ; Kim, Dong Joon. / Purpurogallin is a novel mitogen-activated protein kinase kinase 1/2 inhibitor that suppresses esophageal squamous cell carcinoma growth in vitro and in vivo. In: Molecular Carcinogenesis. 2019 ; Vol. 58, No. 7. pp. 1248-1259.
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AU - Kim, Dong Joon

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