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Clin Cancer Res. 2011 Jul 1;17(13):4414-24. doi: 10.1158/1078-0432.CCR-11-0431. Epub 2011 May 23.

Natura-alpha targets forkhead box m1 and inhibits androgen-dependent and -independent prostate cancer growth and invasion.

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1
Department of Pathology, New York University School of Medicine, New York, New York, USA.

Erratum in

  • Clin Cancer Res. 2011 Sep 1;17(17):5838.
  • Clin Cancer Res. 2011 Jul 1;17(13):OF1.

Abstract

PURPOSE:

The development of new effective therapeutic agents with minimal side effects for prostate cancer (PC) treatment is much needed. Indirubin, an active molecule identified in the traditional Chinese herbal medicine-Qing Dai (Indigo naturalis), has been used to treat leukemia for decades. However, the anticancer properties of Natura-alpha, an indirubin derivative, are not well studied in solid tumors, particularly in PC.

EXPERIMENTAL DESIGN:

The growth kinetics and invasion ability of on human PC cell lines with or without Natura-alpha treatment were measured by cell proliferation and invasion assays. The antitumor effects of Natura-alpha were examined in nude mice tumor xenograft models, and in a patient with advanced hormone-refractory metastatic PC. Signal network proteins targeted by Natura-alpha were analyzed by using proteomic pathway array analysis (PPAA) on xenografts.

RESULTS:

Natura-alpha inhibited the growth of both androgen-dependent (LNCaP) and androgen-independent (LNCaP-AI, PC-3, and DU145) PC cells with IC(50) between 4 to 10 mmol/L, and also inhibited invasion of androgen-independent PC cells. Its antitumor effects were further evident in in vivo tumor reduction in androgen-dependent and androgen-independent nude mice tumor xenograft models and reduced tumor volume in the patient with hormone refractory metastatic PC. PPAA revealed that antiproliferative and antiinvasive activities of Natura-alpha on PC might primarily be through its downregulation of Forkhead box M1 (FOXM1) protein. Forced overexpression of FOXM1 largely reversed the inhibition of growth and invasion by Natura-alpha.

CONCLUSION:

Natura-alpha could serve as a novel and effective therapeutic agent for treatment of both hormone-sensitive and hormone-refractory PC with minimal side effects.

PMID:
21606178
PMCID:
PMC3196615
DOI:
10.1158/1078-0432.CCR-11-0431
[Indexed for MEDLINE]
Free PMC Article
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