A 5′ AMP-Activated Protein Kinase Enzyme Activator, Compound 59, Induces Autophagy and Apoptosis in Human Oral Squamous Cell Carcinoma
Weng, Jing Ru; Dokla, Eman; Bai, Li Yuan; Chen, Ching Shih; Chiu, Shih Jiuan; Shieh, Tzong Ming;
Abstract
5′ AMP-activated protein kinase enzyme (AMPK), a master regulator of cellular metabolism, is recognized for its association with various metabolic diseases, inflammation and cancer. In this study, we aimed to investigate the role of compound 59, an AMPK activator, in a panel of oral squamous cell carcinoma (OSCC) cell lines. The antiproliferative effects of compound 59 were assessed by MTT assays, flow cytometry, Western blotting, confocal microscopy and transmission electron microscopy. Relative to OSCC cells, normal human oral keratinocytes were almost insensitive to compound 59 treatment. Compound 59 induced apoptosis as indicated by caspase activation and PARP cleavage. In addition, it inhibited JAK/STAT3 signalling, arrested cells in the G1 phase, increased reactive oxygen species (ROS) generation and promoted autophagy. Interestingly, pre-treatment with a protein tyrosine phosphatase (PP2A) inhibitor, cantharidin, partially reversed compound 59-induced down-regulation of p-JAK2 and p-STAT3, thereby suggesting the involvement of a protein tyrosine phosphatase. Together, these findings substantiate the potential of compound 59 for the treatment of OSCC patients.
Other data
Title | A 5′ AMP-Activated Protein Kinase Enzyme Activator, Compound 59, Induces Autophagy and Apoptosis in Human Oral Squamous Cell Carcinoma | Authors | Weng, Jing Ru; Dokla, Eman ; Bai, Li Yuan; Chen, Ching Shih; Chiu, Shih Jiuan; Shieh, Tzong Ming | Issue Date | 1-Jul-2018 | Journal | Basic and Clinical Pharmacology and Toxicology | Volume | 123 | Issue | 1 | Start page | 21 | End page | 29 | ISSN | 17427835 | DOI | 10.1111/bcpt.12976 | PubMed ID | 29394526 | Scopus ID | 2-s2.0-85044524815 |
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