A novel pyruvate kinase M2 activator compound that suppresses lung cancer cell viability under hypoxia = 저산소 상태에서 폐암 생장을 억제하는 신규 피루베이트 카이네이즈 M2 활성물질

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Title
A novel pyruvate kinase M2 activator compound that suppresses lung cancer cell viability under hypoxia = 저산소 상태에서 폐암 생장을 억제하는 신규 피루베이트 카이네이즈 M2 활성물질
Author(s)
Dong Joon Kim; Young Soo Park; N D Kim; S H Min; Yeon Mi You; Yuri Jung; Han Koo; Hanmi Noh; Jung Ae KimKyung Chan ParkYoung Il Yeom
Bibliographic Citation
Molecules and Cells, vol. 38, no. 4, pp. 373-379
Publication Year
2015
Abstract
Pyruvate kinase M2 isoform (PKM2), a rate-limiting enzyme in the final step of glycolysis, is known to be associated with the metabolic rewiring of cancer cells, and considered an important cancer therapeutic target. Herein, we report a novel PKM2 activator, PA-12, which was identified via the molecular docking-based virtual screening. We demonstrate that PA-12 stimulates the pyruvate kinase activity of recombinant PKM2 in vitro, with a half-maximal activity concentration of 4.92 μM, and effectively suppresses both anchorage-dependent and -independent growth of lung cancer cells in non-essential amino acid-depleted medium. In addition, PA-12 blocked the nuclear translocalization of PKM2 in lung cancer cells, resulting in the inhibition of hypoxia response element (HRE)-mediated reporter activity as well as hypoxia-inducible factor 1 (HIF-1) target gene expression, eventually leading to the suppression of cell viability under hypoxia. We also verified that the effects of PA-12 were dependent on PKM2 expression in cancer cells, demonstrating the specificity of PA-12 for PKM2 protein. Taken together, our data suggest that PA-12 is a novel and potent PKM2 activator that has therapeutic implications for lung cancer.
Keyword
hypoxialung cancerPA-12PKM2 activator
ISSN
1016-8478
Publisher
Korea Soc-Assoc-Inst
DOI
http://dx.doi.org/10.14348/molcells.2015.2314
Type
Article
Appears in Collections:
Aging Convergence Research Center > 1. Journal Articles
Division of Biomedical Research > Personalized Genomic Medicine Research Center > 1. Journal Articles
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