Abstract

Gallotannin (GT) and GT-enriched extracts derived from various sources are reported to have anti-tumor activity in esophageal, colon and prostate tumors, although their anti-tumor effects have not been determined in lung carcinomas. To investigate the anti-tumor activity of GT-enriched extract of galla rhois (GEGR) against lung carcinomas, alterations in the cytotoxicity, apoptosis activation, cell cycle progression, migration ability, tumor growth, histopathological structure, and the regulation of signaling pathways were analyzed in Lewis lung carcinoma (LLC1) cells and LLC1 tumor bearing C57BL/6NKorl mice, after exposure to GEGR. A high concentration of GT (69%) and DPPH scavenging activity (IC50=7.922 µg/ml) was obtained in GEGR. GEGR treatment exerted strong cytotoxicity, cell cycle arrest at the G2/M phase and subsequent activation of apoptosis, as well as inhibitory effects on the MAPK pathway and PI3K/AKT mediated cell migration in LLC1 cells. In the in vivo syngeneic model, exposure to GEGR resulted in suppressed growth of the LLC1 tumors, as well as inhibition of NF-κB signaling and their inflammatory cytokines. Taken together, our results provide novel evidence that exposure to GEGR induces activation of apoptosis, cell cycle arrest, and inhibition of cell migration via suppression of the MAPK, NF-κB and PI3K/AKT signaling pathways in LLC1 cells and the LLC1 syngeneic model.

Highlights

  • Gallotannins (GT) are found in various plants including Rhus sp., Caesalpinia sp. and Quercus sp., and are formed as a polymer when gallic acid esterifies and conjugates with the hydroxyl group (OH) of a polyol carbohydrate [1]

  • Our results provide novel data which indicates that the anti-tumor activity of GT-enriched extract of galla rhois (GEGR) is associated with the inhibition of MAPK, NK-κB and PI3K/AKT signaling pathways during the development of lung carcinoma

  • These results indicate that GEGR exerts strong free radical scavenging activity, and has the potential for application as an anti-tumor drug with high antioxidant activity

Read more

Summary

Introduction

Gallotannins (GT) are found in various plants including Rhus sp., Caesalpinia sp. and Quercus sp., and are formed as a polymer when gallic acid esterifies and conjugates with the hydroxyl group (OH) of a polyol carbohydrate [1]. GT and its monomer (Gallic acid) are reported to have anti-tumor, antioxidant, anti-inflammatory, antiviral and antiproliferative activities [2,3,4,5,6], but there are limited studies investigating the anti-tumor effects. GT is reported to exert significant anti-tumor effects on NF-κB signaling and inflammatory cytokines in human colon cancer cells, and inhibit the growth of xenograft tumors in NOD/SCID mice [6]. The anti-tumor activity of gallic acid derived from various sources has been reported in tumor cells and xenograft tumor models. Some significant alterations in apoptosis activation and tumor growth suppression have been observed in lung carcinoma cells and xenograft tumor models [14]. The anti-tumor effect and mechanism of GT derived from Galla Rhois (GR) against lung carcinoma cells have never been studied till date

Methods
Results
Discussion
Conclusion
Full Text
Published version (Free)

Talk to us

Join us for a 30 min session where you can share your feedback and ask us any queries you have

Schedule a call