2′-hydroxycinnamaldehyde inhibits cancer cell proliferation and tumor growth by targeting the pyruvate kinase M2 = 하드록시 신남알데하이드에 의한 PKM2 활성화와 항암효과

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Title
2′-hydroxycinnamaldehyde inhibits cancer cell proliferation and tumor growth by targeting the pyruvate kinase M2 = 하드록시 신남알데하이드에 의한 PKM2 활성화와 항암효과
Author(s)
Yae Jin Yoon; Young Hwan Kim; Yena Jin; Seung-Wook ChiJeong Hee MoonDong Cho HanByoung-Mog Kwon
Bibliographic Citation
Cancer Letters, vol. 434, no. 1, pp. 42-55
Publication Year
2018
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.
Keyword
Anti-tumorCancer metabolismExtracellular vesiclePyruvate kinase M2Traditional medicine
ISSN
0304-3835
Publisher
Elsevier
DOI
http://dx.doi.org/10.1016/j.canlet.2018.07.015
Type
Article
Appears in Collections:
Division of Biomedical Research > 1. Journal Articles
Division of Biomedical Research > Disease Target Structure Research Center > 1. Journal Articles
Division of Biomedical Research > Personalized Genomic Medicine Research Center > 1. Journal Articles
Division of Biomedical Research > Genome Editing Research Center > 1. Journal Articles
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