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

Sudhakar Chintharlapalli, Sabitha Papineni, Shashi K. Ramaiah, Stephen Safe

Research output: Contribution to journalArticle

243 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)2816-2823
Number of pages8
JournalCancer research
Volume67
Issue number6
DOIs
StatePublished - Mar 15 2007
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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