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Title: Metabolomics reveals that dietary xenoestrogens alter cellular metabolism induced by palbociclib/letrozole combination cancer therapy
Authors: Warth, Benedikt
Raffeiner, Philipp
Granados, Ana
Huan, Tao
Fang, Mingliang
Forsberg, Erica M.
Benton, H. Paul
Goetz, Laura
Johnson, Caroline H.
Siuzdak, Gary
Keywords: Science::Biological sciences
Issue Date: 2018
Source: Warth, B., Raffeiner, P., Granados, A., Huan, T., Fang, M., Forsberg, E. M., . . . Siuzdak, G. (2018). Metabolomics reveals that dietary xenoestrogens alter cellular metabolism induced by palbociclib/letrozole combination cancer therapy. Cell Chemical Biology, 25(3), 291-300. doi:10.1016/j.chembiol.2017.12.010
Journal: Cell Chemical Biology
Abstract: Recently, the palbociclib/letrozole combination therapy was granted accelerated US FDA approval for the treatment of estrogen receptor (ER)-positive breast cancer. Since the underlying metabolic effects of these drugs are yet unknown, we investigated their synergism at the metabolome level in MCF-7 cells. As xenoestrogens interact with the ER, we additionally aimed at deciphering the impact of the phytoestrogen genistein and the estrogenic mycotoxin zearalenone. A global metabolomics approach was applied to unravel metabolite and pathway modifications. The results clearly showed that the combined effects of palbociclib and letrozole on cellular metabolism were far more pronounced than that of each agent alone and potently influenced by xenoestrogens. This behavior was confirmed in proliferation experiments and functional assays. Specifically, amino acids and central carbon metabolites were attenuated, while higher abundances were observed for fatty acids and most nucleic acid-related metabolites. Interestingly, exposure to model xenoestrogens appeared to counteract these effects.
ISSN: 2451-9456
DOI: 10.1016/j.chembiol.2017.12.010
Rights: © 2017 Elsevier Ltd. All rights reserved.
Fulltext Permission: none
Fulltext Availability: No Fulltext
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