Asiatic Acid Induces Endoplasmic Reticulum Stress and Activates the Grp78/IRE1α/JNK and Calpain Pathways to Inhibit Tongue Cancer Growth.

Jialin Li,Keqiang Huang,Chunyu Ma,Jianhua Huang,Kan Chen,Dongqing Chu,Miaomiao Tian

doi:10.3389/fphar.2021.690612

Abstract

Asiatic acid (AA) has been shown to induce apoptotic death in a range of cancers, but the mechanisms whereby it can inhibit tongue cancer growth have yet to be clarified. Herein, we explored the effects of AA on tongue cancer cells and found that it induced their apoptotic death in vitro and in vivo, while additionally impairing xenograft tumor growth in vivo. From a mechanistic perspective, AA treatment was associated with increases in levels of calcium and the calcium- dependent protease calpain, and it further induced endoplasmic reticulum (ER) stress and consequent Grp78-related IRE1α and JNK phosphorylation, ultimately driving caspase-3 activation and apoptotic death. Together, these results highlight AA as a promising tool for the therapeutic treatment of tongue cancer in clinical practice.

Highlights

Tongue cancer is the most common form of oral cancer in the world and can manifest along the back, base, and edge of the tongue in affected individuals
We began by assessing the impact of Asiatic acid (AA) on tongue cancer cell viability via an MTT assay, which revealed that AA application significantly suppressed the viability of these cells with an IC50 value of approximately 40°μM (Figure 1A)
To confirm the induction apoptosis in tongue cancer cells following AA treatment, mitochondrial apoptotic pathway related-protein levels were assessed via Western blotting

Summary

Introduction

Tongue cancer is the most common form of oral cancer in the world and can manifest along the back, base, and edge of the tongue in affected individuals This type of malignancy is associated with a poor prognosis owing to its high recurrence rates and tendency to exhibit aggressive growth (Xie et al, 2014; Taghavi and Yazdi, 2015), with approximately half of affected patients initially presenting with advanced disease. As our preliminary studies have suggested that AA is capable of inhibitingtongue cancer cell growth, we Asiatic acid inhibits ER Stress conducted the present study in an effort to better understand the mechanistic basis for the anti-cancer activity of this promising therapeutic compound

Methods

Results

Conclusion