Progesterone inhibits the growth of human neuroblastoma

in vitro and in vivo evidence.

Fahim Atif, Iqbal Sayeed, Seema Yousuf, Tauheed Ishrat, Fang Hua, Jun Wang, Daniel J. Brat, Donald G. Stein

Research output: Contribution to journalArticle

18 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1084-1094
Number of pages11
JournalMolecular medicine (Cambridge, Mass.)
Volume17
Issue number9-10
StatePublished - Jan 1 2011

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Neuroblastoma
Progesterone
Growth
Matrix Metalloproteinases
Biological Availability
Finasteride
Safety
Foreskin
Neurons
Neoplasms
Matrix Metalloproteinase 9
Proliferating Cell Nuclear Antigen
Drug-Related Side Effects and Adverse Reactions
Heterografts
Nude Mice
Caspase 3
Vascular Endothelial Growth Factor A
Blood Vessels
Cell Survival
Oxidoreductases

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Genetics(clinical)

Cite this

Atif, F., Sayeed, I., Yousuf, S., Ishrat, T., Hua, F., Wang, J., ... Stein, D. G. (2011). Progesterone inhibits the growth of human neuroblastoma: in vitro and in vivo evidence. Molecular medicine (Cambridge, Mass.), 17(9-10), 1084-1094.

Progesterone inhibits the growth of human neuroblastoma : in vitro and in vivo evidence. / Atif, Fahim; Sayeed, Iqbal; Yousuf, Seema; Ishrat, Tauheed; Hua, Fang; Wang, Jun; Brat, Daniel J.; Stein, Donald G.

In: Molecular medicine (Cambridge, Mass.), Vol. 17, No. 9-10, 01.01.2011, p. 1084-1094.

Research output: Contribution to journalArticle

Atif, F, Sayeed, I, Yousuf, S, Ishrat, T, Hua, F, Wang, J, Brat, DJ & Stein, DG 2011, 'Progesterone inhibits the growth of human neuroblastoma: in vitro and in vivo evidence.', Molecular medicine (Cambridge, Mass.), vol. 17, no. 9-10, pp. 1084-1094.
Atif, Fahim ; Sayeed, Iqbal ; Yousuf, Seema ; Ishrat, Tauheed ; Hua, Fang ; Wang, Jun ; Brat, Daniel J. ; Stein, Donald G. / Progesterone inhibits the growth of human neuroblastoma : in vitro and in vivo evidence. In: Molecular medicine (Cambridge, Mass.). 2011 ; Vol. 17, No. 9-10. pp. 1084-1094.
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