Betulinic acid inhibits prostate cancer growth through inhibition of specificity protein transcription factors | Academic Article individual record
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.

authors
author list (cited authors)
Chintharlapalli, S., Papineni, S., Ramaiah, S. K., & Safe, S.
publication date
2007
published in
keywords
  • Sp4 Transcription Factor
  • Survivin
  • Liver
  • Xenograft Model Antitumor Assays
  • Inhibitor Of Apoptosis Proteins
  • Sp3 Transcription Factor
  • Neovascularization, Pathologic
  • Angiogenesis Inhibitors
  • Triterpenes
  • Neoplasm Proteins
  • Sp Transcription Factors
  • Cell Line, Tumor
  • Proteasome Endopeptidase Complex
  • Prostatic Neoplasms
  • Sp1 Transcription Factor
  • Promoter Regions, Genetic
  • Vascular Endothelial Growth Factor A
  • Microtubule-Associated Proteins
  • Mice, Nude
  • Mice
  • Apoptosis
  • Humans
  • Male
  • Animals
  • Cell Growth Processes
  • Antineoplastic Agents, Phytogenic