Abstract | PURPOSE: MATERIALS AND METHODS: RESULTS: (i) FND-4b increased AMPK activation with concomitant decreases in ACC activity, phosphorylated S6, and cyclin D1 in all subtypes. (ii) FND-4b decreased proliferation in all cells, while dose-dependent growth decreases were found in ER+BC and TNBC. (iii) Increases in apoptosis were observed in ER+BC and the MDA-MB-231 cell line with FND-4b treatment. CONCLUSIONS: Our findings indicate that FND-4b decreases proliferation for a variety of breast cancers by activating AMPK and has notable effects on TNBC. The growth reductions were mediated through decreases in fatty acid synthesis (ACC), mTOR signaling (S6), and cell cycle flux ( cyclin D1). ER+BC cells were more susceptible to FND-4b-induced apoptosis, but MDA-MB-231 cells still underwent apoptosis with higher dose treatment. Further development of FND compounds could result in a novel therapeutic for TNBC.
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Authors | Jeremy Johnson, Piotr Rychahou, Vitaliy M Sviripa, Heidi L Weiss, Chunming Liu, David S Watt, B Mark Evers |
Journal | PloS one
(PLoS One)
Vol. 14
Issue 3
Pg. e0209392
( 2019)
ISSN: 1932-6203 [Electronic] United States |
PMID | 30875375
(Publication Type: Journal Article, Research Support, N.I.H., Extramural)
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Chemical References |
- CCND1 protein, human
- Phenylurea Compounds
- Receptors, Estrogen
- Ribosomal Protein S6
- Cyclin D1
- Poly(ADP-ribose) Polymerases
- AMP-Activated Protein Kinases
- Acetyl-CoA Carboxylase
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Topics |
- AMP-Activated Protein Kinases
(metabolism)
- Acetyl-CoA Carboxylase
(metabolism)
- Cell Line, Tumor
- Cell Proliferation
(drug effects)
- Cell Survival
(drug effects)
- Cyclin D1
(metabolism)
- Enzyme Activation
(drug effects)
- Female
- Gene Expression Regulation, Neoplastic
(drug effects)
- Humans
- MCF-7 Cells
- Phenylurea Compounds
(pharmacology)
- Poly(ADP-ribose) Polymerases
(metabolism)
- Receptors, Estrogen
(metabolism)
- Ribosomal Protein S6
(metabolism)
- Triple Negative Breast Neoplasms
(drug therapy, metabolism)
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