Metabolomics reveals that dietary xenoestrogens alter cellular metabolism induced by palbociclib/letrozole combination cancer therapy
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...
| Main Authors: | , , , , , , , , , |
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| Other Authors: | |
| Format: | Journal Article |
| Language: | English |
| Published: |
2020
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| Online Access: | https://hdl.handle.net/10356/139116 |
| _version_ | 1826115516511551488 |
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| author | Warth, Benedikt Raffeiner, Philipp Granados, Ana Huan, Tao Fang, Mingliang Forsberg, Erica M. Benton, H. Paul Goetz, Laura Johnson, Caroline H. Siuzdak, Gary |
| author2 | School of Civil and Environmental Engineering |
| author_facet | School of Civil and Environmental Engineering Warth, Benedikt Raffeiner, Philipp Granados, Ana Huan, Tao Fang, Mingliang Forsberg, Erica M. Benton, H. Paul Goetz, Laura Johnson, Caroline H. Siuzdak, Gary |
| author_sort | Warth, Benedikt |
| collection | NTU |
| description | 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. |
| first_indexed | 2024-10-01T03:56:27Z |
| format | Journal Article |
| id | ntu-10356/139116 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T03:56:27Z |
| publishDate | 2020 |
| record_format | dspace |
| spelling | ntu-10356/1391162020-05-15T08:34:14Z Metabolomics reveals that dietary xenoestrogens alter cellular metabolism induced by palbociclib/letrozole combination cancer therapy Warth, Benedikt Raffeiner, Philipp Granados, Ana Huan, Tao Fang, Mingliang Forsberg, Erica M. Benton, H. Paul Goetz, Laura Johnson, Caroline H. Siuzdak, Gary School of Civil and Environmental Engineering Science::Biological sciences Combinatory Chemotherapy Ibrance 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. 2020-05-15T08:34:14Z 2020-05-15T08:34:14Z 2018 Journal Article 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 2451-9456 https://hdl.handle.net/10356/139116 10.1016/j.chembiol.2017.12.010 29337187 2-s2.0-85040322941 3 25 291 300 en Cell Chemical Biology © 2017 Elsevier Ltd. All rights reserved. |
| spellingShingle | Science::Biological sciences Combinatory Chemotherapy Ibrance Warth, Benedikt Raffeiner, Philipp Granados, Ana Huan, Tao Fang, Mingliang Forsberg, Erica M. Benton, H. Paul Goetz, Laura Johnson, Caroline H. Siuzdak, Gary Metabolomics reveals that dietary xenoestrogens alter cellular metabolism induced by palbociclib/letrozole combination cancer therapy |
| title | Metabolomics reveals that dietary xenoestrogens alter cellular metabolism induced by palbociclib/letrozole combination cancer therapy |
| title_full | Metabolomics reveals that dietary xenoestrogens alter cellular metabolism induced by palbociclib/letrozole combination cancer therapy |
| title_fullStr | Metabolomics reveals that dietary xenoestrogens alter cellular metabolism induced by palbociclib/letrozole combination cancer therapy |
| title_full_unstemmed | Metabolomics reveals that dietary xenoestrogens alter cellular metabolism induced by palbociclib/letrozole combination cancer therapy |
| title_short | Metabolomics reveals that dietary xenoestrogens alter cellular metabolism induced by palbociclib/letrozole combination cancer therapy |
| title_sort | metabolomics reveals that dietary xenoestrogens alter cellular metabolism induced by palbociclib letrozole combination cancer therapy |
| topic | Science::Biological sciences Combinatory Chemotherapy Ibrance |
| url | https://hdl.handle.net/10356/139116 |
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