Biological and clinical effects of abiraterone on anti-resorptive and anabolic activity in bone microenvironment

Michele Iuliani; Francesco Pantano; Consuelo Buttigliero; Marco Fioramonti; Valentina Bertaglia; Bruno Vincenzi; Alice Zoccoli; Giulia Ribelli; Marcello Tucci; Francesca Vignani; Alfredo Berruti; Giorgio Vittorio Scagliotti; Giuseppe Tonini; Daniele Santini

doi:10.18632/oncotarget.3724

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Research Papers:

Biological and clinical effects of abiraterone on anti-resorptive and anabolic activity in bone microenvironment

Michele Iuliani, Francesco Pantano, Consuelo Buttigliero, Marco Fioramonti, Valentina Bertaglia, Bruno Vincenzi, Alice Zoccoli, Giulia Ribelli, Marcello Tucci, Francesca Vignani, Alfredo Berruti, Giorgio Vittorio Scagliotti, Giuseppe Tonini and Daniele Santini _

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Oncotarget. 2015; 6:12520-12528. https://doi.org/10.18632/oncotarget.3724

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Abstract

Michele Iuliani1,*, Francesco Pantano1,*, Consuelo Buttigliero2, Marco Fioramonti1, Valentina Bertaglia2, Bruno Vincenzi1, Alice Zoccoli1, Giulia Ribelli1, Marcello Tucci2, Francesca Vignani2, Alfredo Berruti3, Giorgio Vittorio Scagliotti2, Giuseppe Tonini1 and Daniele Santini1

1 Translational Oncology Laboratory, Medical Oncology, University Campus Bio-Medico of Rome, Rome, Italy

2 Department of Oncology, University of Turin, San Luigi Hospital, Orbassano, Turin, Italy

3 U.O. Oncologia Medica, Ospedali Civili di Brescia, Brescia, Italy

* These authors have contributed equally to this work

Correspondence to:

Daniele Santini, email:

Keywords: abiraterone acetate, osteoclast, osteoblast, bone marker

Received: February 06, 2015 Accepted: March 03, 2015 Published: March 30, 2015

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.

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Research Papers:

Biological and clinical effects of abiraterone on anti-resorptive and anabolic activity in bone microenvironment

Abstract