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

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.

A New Family of Jumonji C Domain-Containing KDM Inhibitors Inspired by Natural Product Purpurogallin

“…Therefore, efforts to develop new inhibitors able to block KDM4A activity and inhibit cancer cell proliferation are increasing. Purpurogallin 9aa, already described as an antiinflammatory, antioxidant, and anticancer agent (Wu et al, 1996;Kitada et al, 2003;Leone et al, 2003;Sang et al, 2004;Cheng et al, 2012;Xie et al, 2019), was found to be a KDM4A inhibitor. Based on the structure of 9aa, we synthesized a set of derivatives and analogs by changes on the starting phenol ring.…”

“…This compound belongs to the family of benzotropolone-containing natural products (Nierenstein and Swanton, 1944; Barltrop and Nicholson, 1948;Arpin et al, 1974;Klostermeyer et al, 2000;Kerschensteiner et al, 2011;Matsuo et al, 2017) and was already known to display antioxidant (Wu et al, 1996) and anticancer activities (Kitada et al, 2003;Leone et al, 2003), and to play a role in the modulation of inflammatory responses (Sang et al, 2004). Purpurogallin and its synthetic analogs were more recently reported to function as inhibitors of Toll-like receptors 1/2 (Cheng et al, 2012), and to modulate mitogen-activated protein kinase 1/2 signaling pathway, reducing esophageal squamous cell carcinoma growth (Xie et al, 2019).…”

LC-ESI-MS/GC-MS Based Metabolite Profiling of Chlorophytum comosum (Thunb.) Jaques and evaluation of its antioxidant and antiproliferative effects on lung and breast cancer cell lines

“…Chlorphytum comosum (Thunb). Jacques (Spider Ivy) is a well-known plant for its ornamental value worldwide however based on ethanopharmacological evidence it has documented to be used in traditional Chinese medicine preparations for treatment of respiratory ailments, fracture and burns [3][4] [25].Thus, to best of our knowledge our study is the first systematic and comparative profiling of the plant marking the presence of other anticancer active molecules than saponins , however this is the initial screening which needs to be further validated by isolation and characterization studies to find out the lead molecules involved in anticancer therapy.…”

Response surface optimization of polysaccharide extraction from Galla Chinensis and determination of its antioxidant activity in vitro

“…Gallic acid, ellagic acid, β-sitosterol, amentoflavone and purpurogallin were most frequently investigated and considered as the antioxidant compounds of Galla Chinensis. Their protective role in preventing various oxidative damage diseases have widely reported toward the various application potentials in recent years (Chen et al, 2018;Farbood et al, 2019;Kahkeshani et al, 2019;Ponnulakshmi et al, 2019;Xie et al, 2019). However, as the complex plant-insect symbiont, bioactive processes during galls formation suppose to generate abundance of bioactive metabolites in Galla Chinensis.…”