2. Academic Validation
  3. 2'-hydroxycinnamaldehyde inhibits cancer cell proliferation and tumor growth by targeting the pyruvate kinase M2

2'-hydroxycinnamaldehyde inhibits cancer cell proliferation and tumor growth by targeting the pyruvate kinase M2

  • Cancer Lett. 2018 Oct 10;434:42-55. doi: 10.1016/j.canlet.2018.07.015.
Yae Jin Yoon 1,  Young-Hwan Kim 2,  Yena Jin 3,  Seung-Wook Chi 4,  Jeong Hee Moon 5,  Dong Cho Han 6,  Byoung-Mog Kwon 7
Affiliations

Affiliations

  • 1 Laboratory of Chemical Biology and Genomics, Korea Research Institute of Bioscience and Biotechnology, 125 Gwahakro, Daejeon, 34141, Republic of Korea.
  • 2 Laboratory of Chemical Biology and Genomics, Korea Research Institute of Bioscience and Biotechnology, 125 Gwahakro, Daejeon, 34141, Republic of Korea; Department of Biology, Chungnam National University, Daejeon, 34134, Republic of Korea.
  • 3 Laboratory of Chemical Biology and Genomics, Korea Research Institute of Bioscience and Biotechnology, 125 Gwahakro, Daejeon, 34141, Republic of Korea; Korea University of Science and Technology in Korea, Daejeon, 34113, Republic of Korea.
  • 4 Medical Proteomics Research Center, Korea Research Institute of Bioscience and Biotechnology, 125 Gwahakro, Daejeon, 34141, Republic of Korea; Korea University of Science and Technology in Korea, Daejeon, 34113, Republic of Korea.
  • 5 Medical Proteomics Research Center, Korea Research Institute of Bioscience and Biotechnology, 125 Gwahakro, Daejeon, 34141, Republic of Korea.
  • 6 Laboratory of Chemical Biology and Genomics, Korea Research Institute of Bioscience and Biotechnology, 125 Gwahakro, Daejeon, 34141, Republic of Korea; Korea University of Science and Technology in Korea, Daejeon, 34113, Republic of Korea. Electronic address: [email protected].
  • 7 Laboratory of Chemical Biology and Genomics, Korea Research Institute of Bioscience and Biotechnology, 125 Gwahakro, Daejeon, 34141, Republic of Korea; Korea University of Science and Technology in Korea, Daejeon, 34113, Republic of Korea. Electronic address: [email protected].
PMID: 30009856 DOI: 10.1016/j.canlet.2018.07.015
Abstract

It is reported that 2'-hydroxycinnamaldehyde (HCA), isolated from cinnamon, has anti-tumor effects through the modulation of multi-target molecules. In this study, we identified Pyruvate Kinase M2 (PKM2) as a direct target of HCA by use of biochemical methods including affinity chromatography, drug affinity responsive target stability, and cellular thermal shift assay. PKM2 is up-regulated in multiple Cancer types and is considered as a potential target for Cancer therapy. HCA binds directly to PKM2 and selectively decreases the phosphorylation of PKM2 at Tyr105, indicating a potential anti-proliferative effect on prostate Cancer cells. As a PKM2 activator, HCA increases Pyruvate Kinase activity by promoting the tetrameric state of PKM2. However, HCA suppresses protein kinase activity of PKM2 by decreasing the phosphorylation at Tyr105. Moreover, this leads to a decrease of PKM2-mediated STAT3 phosphorylation at Tyr705 and a down-regulation of target genes, including MEK5 and cyclin D1. Furthermore, HCA suppresses tumor growth and the release of tumor extracellular vesicles in vivo by inhibiting the phosphorylation of PKM2. Collectively, our results suggest that HCA may be a potential Anticancer agent targeting PKM2 in Cancer progression.

Keywords

Anti-tumor; Cancer metabolism; Extracellular vesicle; Pyruvate kinase M2; Traditional medicine.

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