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

• Published in: International journal of molecular sciences 2023-06, Vol.24 (12), p.9819
• Main Authors: Shih, Yin-Hwa, Chen, Chieh-Chieh, Kuo, Yueh-Hsiung, Fuh, Lih-Jyh, Lan, Wan-Chen, Wang, Tong-Hong, Chiu, Kuo-Chou, Nguyen, Thanh-Hien Vu, Hsia, Shih-Min, Shieh, Tzong-Ming
• Format: Article
• Language: English
• Subjects: Analysis; Antioxidants; Apoptosis; Autophagy; caffeamide derivative; Caffeic acid; caffeic acid phenethyl ester (CAPE); Caffeic Acids - pharmacology; Cancer; Cancer therapies; Carcinoma, Squamous Cell - drug therapy; Carcinoma, Squamous Cell - pathology; Care and treatment; Cell cycle; Cell death; Cell growth; Cell Line, Tumor; Cytotoxicity; Flow cytometry; Head and Neck Neoplasms; Humans; Kinases; Mediation; Mouth Neoplasms - drug therapy; Oral cancer; Oral carcinoma; Oral squamous cell carcinoma; oral squamous cell carcinoma (OSCC); Oxidative stress; Phenotypes; Phenylethyl Alcohol - pharmacology; Prostate; Protein expression; Proteins; Reactive oxygen species; reactive oxygen species (ROS); S phase; Squamous cell carcinoma; Squamous Cell Carcinoma of Head and Neck; TOR protein; Trends
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms24129819

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 ( , , , , and ) 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 and were more cytotoxic than the other compounds in SAS cells. After or 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, or treatment inhibited malignant phenotypes through mTOR-ULK1-P62-LC3 autophagic signaling activated by ROS generation. These results showed that and induce cancer cell death by activating autophagy signaling, which is correlated with altered cellular oxidative stress.