Betulinic acid inhibits prostate cancer growth through inhibition of specificity protein transcription factors. Academic Article uri icon

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.

published proceedings

  • Cancer Res

altmetric score

  • 3

author list (cited authors)

  • Chintharlapalli, S., Papineni, S., Ramaiah, S. K., & Safe, S.

citation count

  • 244

complete list of authors

  • Chintharlapalli, Sudhakar||Papineni, Sabitha||Ramaiah, Shashi K||Safe, Stephen

publication date

  • March 2007