A 5' AMP-Activated Protein Kinase Enzyme Activator, Compound 59, Induces Autophagy and Apoptosis in Human Oral Squamous Cell Carcinoma

Jing Ru Weng, Eman M.E. Dokla, Li Yuan Bai, Ching Shih Chen, Shih Jiuan Chiu, Tzong Ming Shieh

Research output: Contribution to journalArticle

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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.

LanguageEnglish
JournalBasic and Clinical Pharmacology and Toxicology
DOIs
Publication statusAccepted/In press - Jan 1 2018

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Enzyme Activators
AMP-Activated Protein Kinases
Autophagy
Squamous Cell Carcinoma
Protein Tyrosine Phosphatases
Apoptosis
Cantharidin
Cell signaling
Flow cytometry
Confocal microscopy
Metabolic Diseases
G1 Phase
Caspases
Transmission Electron Microscopy
Keratinocytes
Metabolism
Confocal Microscopy
Assays
Reactive Oxygen Species
Flow Cytometry

ASJC Scopus subject areas

  • Toxicology
  • Pharmacology

Cite this

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 M.E.; Bai, Li Yuan; Chen, Ching Shih; Chiu, Shih Jiuan; Shieh, Tzong Ming.

In: Basic and Clinical Pharmacology and Toxicology, 01.01.2018.

Research output: Contribution to journalArticle

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