Title |
Progesterone Inhibits the Growth of Human Neuroblastoma: In Vitro and In Vivo Evidence
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Published in |
Molecular Medicine, June 2011
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DOI | 10.2119/molmed.2010.00255 |
Pubmed ID | |
Authors |
Fahim Atif, Iqbal Sayeed, Seema Yousuf, Tauheed Ishrat, Fang Hua, Jun Wang, Daniel J. Brat, Donald G. Stein |
Abstract |
We investigated the antitumorogenic effects of progesterone (P4) in a human neuroblastoma (SK-N-AS) cell line in vitro and in a mouse xenograft model of neuroblastoma. The safety of P4 was tested in rat primary cortical neurons and human foreskin fibroblasts (HFF-1). At high doses, P4 significantly (P < 0.05) decreased SK-N-AS cell viability in vitro, and this effect was not blocked either by 5α-reductase inhibitor, finasteride or the P4 receptor antagonist RU486. Even at very high doses, P4 did not induce any cell death in healthy primary cortical neurons or HFF-1. The bioavailability of P4 24 h after the last injection in the serum of treated animals was significantly (P < 0.05) higher (10-33 μg/mL) than in untreated animals. In nude mice, P4 (50 and 100 mg/kg) inhibited neuroblastoma growth by ~50% over 8 d of treatment. No drug toxicity was observed in the mice, as measured by body weight and activity. P4 suppressed the expression of vascular endothelial growth factor (VEGF) and matrix metalloproteinases (MMP-9, MMP-2), which are involved in tumor vascular development. High-dose P4 inhibited tumor growth by suppressing cell proliferation and inducing apoptosis, as evidenced by the expression of proliferating cell nuclear antigen and cleaved caspase-3. P4 significantly increased the expression of P4 receptor isoform-A and suppressed phospho-Akt (Ser437) expression. In conclusion, at high doses, P4 effectively inhibits the growth of solid neuroblastoma tumor and has high bioavailability, selective toxicity and a high margin of safety, making it a possible candidate for further study as a potential clinical treatment of neuroblastoma. |
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Geographical breakdown
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Demographic breakdown
Readers by professional status | Count | As % |
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Researcher | 5 | 15% |
Student > Ph. D. Student | 5 | 15% |
Student > Bachelor | 3 | 9% |
Student > Postgraduate | 3 | 9% |
Other | 3 | 9% |
Unknown | 7 | 21% |
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Chemistry | 1 | 3% |
Other | 0 | 0% |
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