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Fli-1 Activation through Targeted Promoter Activity Regulation Using a Novel 3’, 5’-diprenylated Chalcone Inhibits Growth and Metastasis of Prostate Cancer Cells

by Youfen Ma 1,5,†, Bixue Xu 1,2,†, Jia Yu 1,2, Lirong Huang 4, Xiaoping Zeng 1,2, Xiangchun Shen 1,5, Chunyan Ren 3, Yaacov Ben-David 1,2,* and Heng Luo 1,2,3,*
1
State key laboratory of functions and applications of medicinal plants, Guizhou medical university, Guiyang 550014, China
2
The Key Laboratory of Chemistry for Natural Products of Guizhou Province and Chinese Academy of Science, Guiyang 550014, China
3
Boston Children’s Hospital, Harvard Medical School, Boston, MA 02115, USA
4
College of Food and Pharmaceutical Engineering, Guizhou Institute of Technology, Guiyang 550003, China
5
College of pharmacy, Guizhou Medical University, Guiyang 550029, China
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Int. J. Mol. Sci. 2020, 21(6), 2216; https://doi.org/10.3390/ijms21062216
Received: 12 February 2020 / Revised: 12 March 2020 / Accepted: 17 March 2020 / Published: 23 March 2020
The friend leukemia integration 1 (Fli-1) gene is involved in the expression control of key genes in multiple pathogenic/physiological processes, including cell growth, differentiation, and apoptosis; this implies that Fli-1 is a strong candidate for drug development. In our previous study, a 3′,5′-diprenylated chalcone, (E)-1-(2-hydroxy-4-methoxy-3,5-diprenyl) phenyl-3-(3-pyridinyl)-propene-1-one (C10), was identified as a novel anti-prostate cancer (PCa) agent. Here, we investigated the molecular mechanisms underlying the anti-cancer effects of C10 on the growth, metastasis, and invasion of PC3 cells in vitro. Our results show that C10 exhibited a strong inhibitory effect on proliferation and metastasis of PC3 cells via several cellular and flow cytometric analyses. Further mechanism studies revealed that C10 likely serves as an Fli-1 agonist for regulating the expression of Fli-1 target genes including phosphatidylinositol 3-kinase (P110), murine double minute2 (MDM2), B-cell lymphoma-2 (Bcl-2), Src homology-2 domain-containing inositol 5-phosphatase 1 (SHIP-1), and globin transcription factor-1 (Gata-1) as well as the phosphorylation of extracellular-regulated protein kinases 1 (ERK1). Further, we confirmed that C10 can regulate the expressions of vascular endothelial growth factor 1 (VEGF-1), transforming growth factor-β2 (TGF-β2), intercellular cell adhesion molecule-1 (ICAM-1), p53, and matrix metalloproteinase 1 (MMP-1) genes associated with tumor apoptosis, migration, and invasion. Thus, C10 exhibits stronger anticancer activity with novel molecular targets and regulatory molecular mechanisms, indicating its great potency for development as a novel targeted anticancer drug. View Full-Text
Keywords: prostate cancer; Fli-1 agonist; chalcone; invasion; migration; apoptosis prostate cancer; Fli-1 agonist; chalcone; invasion; migration; apoptosis
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MDPI and ACS Style

Ma, Y.; Xu, B.; Yu, J.; Huang, L.; Zeng, X.; Shen, X.; Ren, C.; Ben-David, Y.; Luo, H. Fli-1 Activation through Targeted Promoter Activity Regulation Using a Novel 3’, 5’-diprenylated Chalcone Inhibits Growth and Metastasis of Prostate Cancer Cells. Int. J. Mol. Sci. 2020, 21, 2216.

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