Molecular Cancer Therapeutics, volume 14, issue 10, pages 2228-2237
Anticancer Properties of a Novel Class of Tetrafluorinated Thalidomide Analogues
Shaunna L. Beedie
1, 2
,
Cody J. Peer
3
,
Steven Pisle
3
,
Erin R. Gardner
3
,
Chris Mahony
2
,
Shelby Barnett
2
,
Agnieszka Ambrożak
4
,
Michael Gütschow
4
,
Cindy H. Chau
1
,
Neil Vargesson
2
,
WILLIAM D. FIGG &NA;
1, 3
1
1Molecular Pharmacology Section, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland.
|
3
3Clinical Pharmacology Program, Genitourinary Malignancies Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland.
|
Publication type: Journal Article
Publication date: 2015-10-01
Journal:
Molecular Cancer Therapeutics
Quartile SCImago
Q1
Quartile WOS
Q2
Impact factor: 5.7
ISSN: 15357163, 15388514
Cancer Research
Oncology
Abstract
Thalidomide has demonstrated clinical activity in various malignancies affecting immunomodulatory and angiogenic pathways. The development of novel thalidomide analogs with improved efficacy and decreased toxicity is an ongoing research effort. We recently designed and synthesized a new class of compounds, consisting of both tetrafluorinated thalidomide analogues (Gu973 and Gu998) and tetrafluorobenzamides (Gu1029 and Gu992). In this study, we demonstrate the antiangiogenic properties of these newly synthesized compounds. We examined the specific antiangiogenic characteristics in vitro using rat aortic rings with carboxyamidotriazole as a positive control. In addition, further in vitro efficacy was evaluated using human umbilical vein endothelial cells (HUVEC) and PC3 cells treated with 5 and 10 μmol/L doses of each compound. All compounds were seen to reduce microvessel outgrowth in rat aortic rings as well as to inhibit HUVECs to a greater extent, at lower concentrations than previously tested thalidomide analogs. The antiangiogenic properties of the compounds were also examined in vivo in fli1:EGFP zebrafish embryos, where all compounds were seen to inhibit the extent of outgrowth of newly developing blood vessels. In addition, Gu1029 and Gu973 reduced the anti-inflammatory response in mpo:GFP zebrafish embryos, whereas Gu998 and Gu992 showed no difference. The compounds' antitumor effects were also explored in vivo using the human prostate cancer PC3 xenograft model. All four compounds were also screened in vivo in chicken embryos to investigate their teratogenic potential. This study establishes these novel thalidomide analogues as a promising immunomodulatory class with anticancer effects that warrant further development to characterize their mechanisms of action. Mol Cancer Ther; 14(10); 2228–37. ©2015 AACR.
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Citations by publishers
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8
9
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Elsevier
9 publications, 30%
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1 publication, 3.33%
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1 publication, 3.33%
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1 publication, 3.33%
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- We do not take into account publications without a DOI.
- Statistics recalculated only for publications connected to researchers, organizations and labs registered on the platform.
- Statistics recalculated weekly.
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Beedie S. L. et al. Anticancer Properties of a Novel Class of Tetrafluorinated Thalidomide Analogues // Molecular Cancer Therapeutics. 2015. Vol. 14. No. 10. pp. 2228-2237.
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Beedie S. L., Peer C. J., Pisle S., Gardner E. R., Mahony C., Barnett S., Ambrożak A., Gütschow M., Chau C. H., Vargesson N., FIGG &NA; W. D. Anticancer Properties of a Novel Class of Tetrafluorinated Thalidomide Analogues // Molecular Cancer Therapeutics. 2015. Vol. 14. No. 10. pp. 2228-2237.
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TY - JOUR
DO - 10.1158/1535-7163.mct-15-0320
UR - https://doi.org/10.1158/1535-7163.mct-15-0320
TI - Anticancer Properties of a Novel Class of Tetrafluorinated Thalidomide Analogues
T2 - Molecular Cancer Therapeutics
AU - Beedie, Shaunna L.
AU - Peer, Cody J.
AU - Pisle, Steven
AU - Gardner, Erin R.
AU - Mahony, Chris
AU - Barnett, Shelby
AU - Ambrożak, Agnieszka
AU - Gütschow, Michael
AU - Chau, Cindy H.
AU - Vargesson, Neil
AU - FIGG &NA;, WILLIAM D.
PY - 2015
DA - 2015/10/01 00:00:00
PB - American Association for Cancer Research (AACR)
SP - 2228-2237
IS - 10
VL - 14
SN - 1535-7163
SN - 1538-8514
ER -
Cite this
BibTex
Copy
@article{2015_Beedie,
author = {Shaunna L. Beedie and Cody J. Peer and Steven Pisle and Erin R. Gardner and Chris Mahony and Shelby Barnett and Agnieszka Ambrożak and Michael Gütschow and Cindy H. Chau and Neil Vargesson and WILLIAM D. FIGG &NA;},
title = {Anticancer Properties of a Novel Class of Tetrafluorinated Thalidomide Analogues},
journal = {Molecular Cancer Therapeutics},
year = {2015},
volume = {14},
publisher = {American Association for Cancer Research (AACR)},
month = {oct},
url = {https://doi.org/10.1158/1535-7163.mct-15-0320},
number = {10},
pages = {2228--2237},
doi = {10.1158/1535-7163.mct-15-0320}
}
Cite this
MLA
Copy
Beedie, Shaunna L., et al. “Anticancer Properties of a Novel Class of Tetrafluorinated Thalidomide Analogues.” Molecular Cancer Therapeutics, vol. 14, no. 10, Oct. 2015, pp. 2228-2237. https://doi.org/10.1158/1535-7163.mct-15-0320.