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.
Bibliographical noteFunding 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
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).
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.
- esophageal squamous cell carcinoma
- mitogen-activated protein kinase kinase
- patient-derived xenograft
PubMed: MeSH publication types
- Journal Article
- Research Support, Non-U.S. Gov't