Abstract | PURPOSE: EXPERIMENTAL DESIGN: RESULTS:
Iron was toxic for all prostate cancer cells. In particular, VCaP, LNCaP, and TRAMP-C2 were highly iron sensitive. Toxicity was mediated by oxidative stress, which primarily affected lipids, promoting ferroptosis. In highly sensitive cells, iron additionally caused protein damage. High-basal iron content and oxidative status defined high iron sensitivity. Bicalutamide- iron combination exacerbated oxidative damage and cell death, triggering protein oxidation also in poorly iron-sensitive DU-145 and PC-3 cells.In vivo, iron reduced tumor growth in TRAMP-C2 and VCaP mice. In PC-3 xenografts, bicalutamide- iron combination caused protein oxidation and successfully impaired tumor expansion while single compounds were ineffective. Macrophages influenced body iron distribution but did not limit the iron effect on tumor expansion. CONCLUSIONS: Our models allow us to dissect the direct iron effect on cancer cells. We demonstrate the proof of principle that iron toxicity inhibits prostate cancer cell proliferation, proposing a novel tool to strengthen antiandrogen treatment efficacy.
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Authors | Jessica Bordini, Federica Morisi, Angela Rita Elia, Paolo Santambrogio, Alessia Pagani, Vito Cucchiara, Paolo Ghia, Matteo Bellone, Alberto Briganti, Clara Camaschella, Alessandro Campanella |
Journal | Clinical cancer research : an official journal of the American Association for Cancer Research
(Clin Cancer Res)
Vol. 26
Issue 23
Pg. 6387-6398
(12 01 2020)
ISSN: 1557-3265 [Electronic] United States |
PMID | 32928793
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | ©2020 American Association for Cancer Research. |
Chemical References |
- Androgen Antagonists
- Anilides
- Nitriles
- Tosyl Compounds
- bicalutamide
- Iron
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Topics |
- Androgen Antagonists
(pharmacology)
- Anilides
(pharmacology)
- Animals
- Apoptosis
- Cell Proliferation
- Drug Synergism
- Humans
- Iron
(pharmacology)
- Male
- Mice
- Nitriles
(pharmacology)
- Prostatic Neoplasms
(drug therapy, pathology)
- Tosyl Compounds
(pharmacology)
- Tumor Cells, Cultured
- Xenograft Model Antitumor Assays
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