Published in
Impact Journals, Oncotarget, 14(6), p. 12520-12528, 2015
АБВ-пресс, Onkourologiâ, 4(11), p. 81
DOI: 10.17650/1726-9776-2015-11-4-81-88
Links
- ORCID
- ORCID
- ORCID
- Impact Journals
- АБВ-пресс | PDF
- [www.ncbi.nlm.nih.gov] | PDF
- [hdl.handle.net] | PDF
- [www.researchgate.net] | PDF
- [www.ncbi.nlm.nih.gov] | PDF
- [oncourology.abvpress.ru] | PDF
- [www.ncbi.nlm.nih.gov] | PDF
- [europepmc.org] | PDF
- [iris.unito.it] | PDF
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Biological and clinical effects of abiraterone on anti-resorptive and anabolic activity in bone microenvironment
,
Consuelo Buttigliero,
Marco Fioramonti,
Valentina Bertaglia,
Bruno Vincenzi ,
Alice Zoccoli,
Giulia Ribelli,
Marcello Tucci,
Francesca Vignani,
Alfredo Berruti,
Scagliotti Gv,
Giorgio Vittorio Scagliotti,
Giuseppe Tonini ,
Daniele Santini
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Abstract
Abiraterone acetate (ABI) is associated not only with a significant survival advantage in both chemotherapy-naive and -treated patients with metastatic castration-resistant prostate cancer (mCRPC), but also with a delay in time to development of Skeletal Related Events and in radiological skeletal progression. These bone benefits may be related to a direct effect on prostate cancer cells in bone or to a specific mechanism directed to bone microenvironment. To test this hypothesis we designed an in vitro study aimed to evaluate a potential direct effect of ABI on human primary osteoclasts/osteoblasts (OCLs/OBLs). We also assessed changes in bone turnover markers, serum carboxy-terminal collagen crosslinks (CTX) and alkaline phosphatase (ALP), in 49 mCRPC patients treated with ABI.Our results showed that non-cytotoxic doses of ABI have a statistically significant inhibitory effect on OCL differentiation and activity inducing a down-modulation of OCL marker genes TRAP, cathepsin K and metalloproteinase-9. Furthermore ABI promoted OBL differentiation and bone matrix deposition up-regulating OBL specific genes, ALP and osteocalcin. Finally, we observed a significant decrease of serum CTX values and an increase of ALP in ABI-treated patients.These findings suggest a novel biological mechanism of action of ABI consisting in a direct bone anabolic and anti-resorptive activity.