Caffeic Acid Phenethyl Ester and Caffeamide Derivatives Suppress Oral Squamous Cell Carcinoma Cells

Abstract

Caffeic acid phenethyl ester (CAPE) contains antibiotic and anticancer activities. Therefore, we aimed to investigate the anticancer properties and mechanisms of CAPE and caffeamide derivatives in the oral squamous cell carcinoma cell (OSCC) lines SAS and OECM-1. The anti-OSCC effects of CAPE and the caffeamide derivatives (26G, 36C, 36H, 36K, and 36M) were evaluated using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide test. Cell cycle and total reactive oxygen species (ROS) production were analyzed using flow cytometry. The relative protein expression of malignant phenotypes was determined via Western blot analysis. The results showed that 26G and 36M were more cytotoxic than the other compounds in SAS cells. After 26G or 36M treatment for 48 h, cell cycle S phase or G2/M phase arrest was induced, and cellular ROS increased at 24 h, and then decreased at 48 h in both cell lines. The expression levels of cell cycle regulatory and anti-ROS proteins were downregulated. In addition, 26G or 36M treatment inhibited malignant phenotypes through mTOR-ULK1-P62-LC3 autophagic signaling activated by ROS generation. These results showed that 26G and 36M induce cancer cell death by activating autophagy signaling, which is correlated with altered cellular oxidative stress.

Isolinderalactone Induces Apoptosis, Autophagy, Cell Cycle Arrest and MAPK Activation through ROS–Mediated Signaling in Colorectal Cancer Cell Lines

“…Blocking autophagy did not reduce ROS generation, which is consistent with our results and places ROS upstream of autophagy. Recently, several reports indicated that anticancer agents induced ROS production followed by activation of autophagy and induction of autophagic cell death in oral squamous cell carcinoma, prostate cancer, and CRC cells [ 26 , 27 , 28 ]. However, the exact mechanism by which autophagy achieves this outcome remains unclear.…”

Combining microfluidic chip and low-attachment culture devices to isolate oral cancer stem cells

“…The protocol was described in previous research. 13 Briefly, cell lysates were denatured using 5x SDS sample loading buffer at 95 °C for 5 min and loaded onto 10% SDS-PAGE gels with approximately 10 μg of total protein per lane. The separated proteins were transferred onto Polyvinylidene difluoride (PVDF) membranes, and subsequent blocking was performed with 5% non-fat dry milk in Tris-buffered saline containing 0.1% Tween 20 for 1 h at room temperature.…”

Arecoline Induces ROS Accumulation, Transcription of Proinflammatory Factors, and Expression of KRT6 in Oral Epithelial Cells

“…mRNA levels were analyzed using the Applied Biosystems StepOnePlus™ Real-Time PCR System (Thermo Fisher Scientific, Waltham, MA, USA). All reactions were performed in triplicate, and relative gene expressions were quantified by normalizing to that of GAPDH and calculated using the 2 −∆∆Ct method [29].…”