2. Academic Validation
  3. Biological Evaluation of Selected Flavonoids as Inhibitors of MNKs Targeting Acute Myeloid Leukemia

Biological Evaluation of Selected Flavonoids as Inhibitors of MNKs Targeting Acute Myeloid Leukemia

  • J Nat Prod. 2020 Oct 23;83(10):2967-2975. doi: 10.1021/acs.jnatprod.0c00516.
Liang-Chieh Chen 1 2,  Han-Li Huang 3 4,  Wei-Chun HuangFu 2 3 5,  Shih-Chung Yen 1,  Sin-Ting Ngo 3,  Yi-Wen Wu 5,  Tony Eight Lin 2 5,  Tzu-Ying Sung 6,  Ssu-Ting Lien 2,  Hui-Ju Tseng 3,  Shiow-Lin Pan 2 3 4 5,  Wei-Jan Huang 3 7 8 9,  Kai-Cheng Hsu 2 3 4 5
Affiliations

Affiliations

  • 1 Warshel Institute for Computational Biology, The Chinese University of Hong Kong (Shenzhen), Shenzhen, Guangdong, People's Republic of China.
  • 2 Graduate Institute of Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan.
  • 3 Ph.D. Program in Biotechnology Research and Development, College of Pharmacy, Taipei Medical University, Taipei, Taiwan.
  • 4 Biomedical Commercialization Center, Taipei Medical University, Taipei, Taiwan.
  • 5 Ph.D. Program for Cancer Molecular Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan.
  • 6 Institute of Bioinformatics and Systems Biology, College of Biological Science and Technology, National Chiao Tung University, Hsinchu, Taiwan.
  • 7 Graduate Institute of Pharmacognosy, College of Pharmacy, Taipei Medical University, Taipei, Taiwan.
  • 8 Ph.D. Program for the Clinical Drug Discovery from Botanical Herbs, College of Pharmacy, Taipei, Taiwan.
  • 9 School of Pharmacy, College of Pharmacy, Taipei Medical University, Taipei, Taiwan.
PMID: 33026809 DOI: 10.1021/acs.jnatprod.0c00516
Abstract

Excessive eIF4E phosphorylation by mitogen-activated protein kinase (MAPK)-interacting kinases 1 and 2 (MNK1 and MNK2; collectively, MNKs) has been associated with oncogenesis. The overexpression of eIF4E in acute myeloid leukemia (AML) is related to Cancer cell growth and survival. Thus, the inhibition of MNKs and eIF4E phosphorylation are potential therapeutic strategies for AML. Herein, a structure-based virtual screening approach was performed to identify potential MNK inhibitors from Natural Products. Three Flavonoids, apigenin, hispidulin, and luteolin, showed MNK2 inhibitory activity with IC50 values of 308, 252, and 579 nM, respectively. A structure-activity relationship analysis was performed to disclose the molecular interactions. Furthermore, luteolin exhibited substantial inhibitory efficacy against MNK1 (IC50 = 179 nM). Experimental results from cellular assays showed that hispidulin and luteolin inhibited the growth of MOLM-13 and MV4-11 AML cells by downregulating eIF4E phosphorylation and arresting the cell cycle at the G0/G1 phase. Therefore, hispidulin and luteolin showed promising results as lead compounds for the potential treatment for AML.

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