Chrysophanol Triggers Cell Death via Unfolded Protein Response and Endoplasmic Reticulum Stress in Oral Cancer FaDu Cells

Oral cancer is a type of head and neck cancer that can be life threatening. Unfolded protein response and endoplasmic reticulum stress play a critical role in carcinogenesis. However, prolonged activation of unfolded protein response also activates apoptosis. Thus, a new treatment strategy maybe activation of extensive unfolded protein response and severe endoplasmic reticulum stress in tumor cells. We examined the pharmacological effects of chrysophanol on an oral cancer cell line FaDu, a hypopharyngeal squamous cell carcinoma specifically for its ability to cause cell death via unfolded protein response and endoplasmic reticulum stress. We measured the expression of binding immunoglobulin protein, C/EBP homologous protein, phosphorylated inositol-requiring enzyme-1 alpha, and activating transcription factor 6 after treatment with chrysophanol in absence or presence of APY29 (an inhibitor of phosphorylated inositol-requiring enzyme-1 alpha). Chrysophanol caused cell death via upregulations of binding immunoglobulin protein that is also known as 78-kDa glucose-regulated protein, C/EBP homologous protein, phosphorylated inositol-requiring enzyme-1 alpha, and activating transcription factor 6. This activity was reversed by APY29. Thus, chrysophanol could be a useful antitumor agent for the management of oral cancer.