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Cancer Res. 2007 Mar 15;67(6):2816-23.

Betulinic acid inhibits prostate cancer growth through inhibition of specificity protein transcription factors.

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1
Institute of Biosciences and Technology, Texas A&M University Health Science Center, Houston, Texas 77843-4466, USA.

Abstract

Betulinic acid is a pentacyclic triterpene natural product initially identified as a melanoma-specific cytotoxic agent that exhibits low toxicity in animal models. Subsequent studies show that betulinic acid induces apoptosis and antiangiogenic responses in tumors derived from multiple tissues; however, the underlying mechanism of action is unknown. Using LNCaP prostate cancer cells as a model, we now show that betulinic acid decreases expression of vascular endothelial growth (VEGF) and the antiapoptotic protein survivin. The mechanism of these betulinic acid-induced antiangiogenic and proapoptotic responses in both LNCaP cells and in tumors is due to activation of selective proteasome-dependent degradation of the transcription factors specificity protein 1 (Sp1), Sp3, and Sp4, which regulate VEGF and survivin expression. Thus, betulinic acid acts as a novel anticancer agent through targeted degradation of Sp proteins that are highly overexpressed in tumors.

PMID:
17363604
DOI:
10.1158/0008-5472.CAN-06-3735
[Indexed for MEDLINE]
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