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A 5′ AMP‐Activated Protein Kinase Enzyme Activator, Compound 59, Induces Autophagy and Apoptosis in Human Oral Squamous Cell Carcinoma
Author(s) -
Weng JingRu,
Dokla Eman M. E.,
Bai LiYuan,
Chen ChingShih,
Chiu ShihJiuan,
Shieh TzongMing
Publication year - 2018
Publication title -
basic and clinical pharmacology and toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.805
H-Index - 90
eISSN - 1742-7843
pISSN - 1742-7835
DOI - 10.1111/bcpt.12976
Subject(s) - ampk , apoptosis , protein tyrosine phosphatase , activator (genetics) , flow cytometry , autophagy , protein kinase a , cancer research , kinase , tyrosine kinase , chemistry , biology , microbiology and biotechnology , signal transduction , biochemistry , receptor
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 / STAT 3 signalling, arrested cells in the G1 phase, increased reactive oxygen species ( ROS ) generation and promoted autophagy. Interestingly, pre‐treatment with a protein tyrosine phosphatase ( PP 2A) inhibitor, cantharidin, partially reversed compound 59‐induced down‐regulation of p‐ JAK 2 and p‐ STAT 3, thereby suggesting the involvement of a protein tyrosine phosphatase. Together, these findings substantiate the potential of compound 59 for the treatment of OSCC patients.