Naringenin induces endoplasmic reticulum stress-mediated cell apoptosis and autophagy in human oral squamous cell carcinoma cells.
Ju-Fang LiuTsung-Ming ChangPo-Han ChenJaster Szu-Wei LinYih-Jeng TsaiHsing-Mei WuChia-Jung LeePublished in: Journal of food biochemistry (2022)
Human oral squamous cell carcinoma (OSCC) has been one of the most common oral cancers owing to high percentage of betel nuts chewers, smokers, and alcohol consumption. With current treatment strategies in OSCC, more than half patients relapse and develop distant metastases with poor prognosis. To overcome the incident, OSCC poses a challenge in current therapies and treatments. Naringenin, a natural flavonoid, has been noted for antitumor effects on various types of cancers; however, the effects of naringenin on OSCC remain bias. In this study, naringenin demonstrated the potential multifunction in human OSCC cells not only leading to cell apoptosis, but also alternating the general function of autophagy, serving as pro-survival mechanism by inducing the endoplasmic reticulum (ER) stress signaling through intracellular reactive oxygen species (ROS) production. In the process of programmed cell death, naringenin induced apoptotic signaling through caspase-cascade, mitochondrial dysfunction, and ER stress by aberrance of Ca 2+ release. In contrast, under the presence of naringenin, the pro-survival has been altered into pro-death to activate the caspases-mediated apoptosis achieving cell death. The cross-function of apoptosis and autophagy has demonstrated the effect of naringenin-induced intracellular ROS activity in OSCC cells. Therefore, this study found that the effect of naringenin induces intracellular ROS to trigger programmed cell death and ER stress through the mechanisms of apoptosis and autophagy in human oral squamous carcinoma. PRACTICAL APPLICATIONS: This study revealed that naringenin debilitated the OSCC cell viability via the intracellular ROS production, ER stress, and autophagy, leading to cell apoptosis. Based on these studies and findings, naringenin provided an antitumor effect as a novel natural compound to improve the current therapies in OSCC.
Keyphrases
- cell death
- cell cycle arrest
- endoplasmic reticulum stress
- induced apoptosis
- reactive oxygen species
- endothelial cells
- poor prognosis
- oxidative stress
- high glucose
- cell proliferation
- pluripotent stem cells
- long non coding rna
- induced pluripotent stem cells
- signaling pathway
- endoplasmic reticulum
- alcohol consumption
- dna damage
- magnetic resonance
- end stage renal disease
- high grade
- prognostic factors
- cardiovascular disease
- diabetic rats
- ejection fraction
- squamous cell
- young adults
- free survival
- childhood cancer
- chronic kidney disease
- newly diagnosed
- low grade
- human health
- risk assessment