Archive for the ‘feverfew (parthenolide)’ Category

Restoring chemotherapy and hormone therapy sensitivity by parthenolide in a xenograft hormone refractory prostate cancer model

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Posted 15 Jul 2011 — by James Street
Category feverfew (parthenolide), Prostate Cancer
  1. Rajasubramaniam Shanmugam1,
  2. Vetrichelvan Jayaprakasan1,
  3. Yesim Gokmen-Polar1,
  4. Stephanie Kelich2,
  5. Kathy D. Miller1,
  6. Michele Yip-Schneider3,
  7. Liang Cheng4,
  8. Poornima Bhat-Nakshatri2,
  9. George W. Sledge Jr.1,
  10. Harikrishna Nakshatri2,3,5,
  11. Qi-Huang Zheng6,
  12. Michael A. Miller6,
  13. Timothy DeGrado6,
  14. Gary D. Hutchins6,
  15. Christopher J. Sweeney1,*

Article first published online: 18 AUG 2006

DOI: 10.1002/pros.20482

Keywords:

  • parthenolide;
  • anti-tumor;
  • angiogenesis;
  • NFκB

Abstract

BACKGROUND

Nuclear Factor kappa B (NFκB) is a eukaryotic transcription factor that is constitutively active in human cancers and can be inhibited by the naturally occurring sesquiterpene lactone, parthenolide (P).

METHODS

The in vitro effects of P were assessed using the androgen independent cell line, CWR22Rv1, and human umbilical endothelial cells (HUVECs). The in vivo activity of P as a single agent and its ability to augment the efficacy of docetaxel and the anti-androgen, bicalutamide, were determined using the CWR22Rv1 xenograft model.

RESULTS

Parthenolide at low micromolar concentration inhibited proliferation of CWR22Rv1 and HUVEC cells, promoted apoptosis and abrogated NFκB-DNA binding. Parthenolide downregulated anti-apoptotic genes under NFκB control, TRAF 1 and 2, and promoted sustained activation of c-jun-NH2 kinase (JNK). Parthenolide also augmented the in vivo efficacy of docetaxel and restored sensitivity to anti-androgen therapy.

CONCLUSION

These studies demonstrate parthenolide’s anti-tumor and anti-angiogenic activity, and its potential to augment the efficacy of chemotherapy and hormonal therapy. Prostate 66: 1498–1511, 2006. © 2006 Wiley-Liss, Inc.