2. Academic Validation
  3. A PKM2 inhibitor induces apoptosis and autophagy through JAK2 in human oral squamous cell carcinoma cells

A PKM2 inhibitor induces apoptosis and autophagy through JAK2 in human oral squamous cell carcinoma cells

  • Chem Biol Interact. 2023 Aug 1;380:110538. doi: 10.1016/j.cbi.2023.110538.
Jing-Ru Weng 1,  Balraj Gopula 2,  Po-Chen Chu 3,  Jing-Lan Hu 4,  Chia-Hsien Feng 5
Affiliations

Affiliations

  • 1 Department of Marine Biotechnology and Resources, National Sun Yat-sen University, Kaohsiung, 80424, Taiwan; Graduate Institute of Natural Products, Kaohsiung Medical University, Kaohsiung, 80708, Taiwan; Graduate Institute of Pharmacognosy, College of Pharmacy, Taipei Medical University, Taipei, 11042, Taiwan. Electronic address: jrweng@mail.nsysu.edu.tw.
  • 2 Drug Development Center, China Medical University, Taichung, 40402, Taiwan; Pharmacology & Chemical Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX, 77030, USA.
  • 3 Department of Cosmeceutics and Graduate Institute of Cosmeceutics, China Medical University, Taichung, 40604, Taiwan.
  • 4 Department of Marine Biotechnology and Resources, National Sun Yat-sen University, Kaohsiung, 80424, Taiwan.
  • 5 Department of Fragrance and Cosmetic Science, College of Pharmacy, Kaohsiung Medical University, Kaohsiung, 80708, Taiwan.
PMID: 37164279 DOI: 10.1016/j.cbi.2023.110538
Abstract

The enzyme Pyruvate Kinase M2 (PKM2) is involved in glycolysis, which plays an important role in the regulation of tumor progression. In this study, we investigated the anti-tumor activity of N-(4-(3-(3-(methylamino)-3-oxopropyl)-5-(4'-(trifluoromethyl)-[1,1'-biphenyl]-4-yl)-1H-pyrazol-1-yl)phenyl)propiolamide (MTP), a PKM2 inhibitor, in oral squamous cell carcinoma (OSCC) cells. Our results showed that MTP inhibited cell growth with IC50 values of 0.59 μM and 0.78 μM in SCC2095 and HSC-3 OSCC cells, respectively. MTP induced caspase-dependent Apoptosis, which was associated with the modulation of PKM2 and oncogenic biomarkers epidermal growth factor receptor and β-catenin. In addition, MTP increased the generation of Reactive Oxygen Species (ROS) and modulated the expression of autophagic gene products, including LC3B-II and p62. Western blotting showed that MTP inhibited Janus kinase 2 (JAK2) signaling, and JAK2 overexpression partially reversed MTP-mediated cytotoxicity. Taken together, these data indicate the potential use of MTP as a therapeutic agent for OSCC.

Keywords

Apoptosis; Autophagy; JAK2; OSCC; PKM2; ROS.

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