Related Experiment Video
Updated: Aug 6, 2026
A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer
Published on: March 6, 2018
Restoring chemotherapy and hormone therapy sensitivity by parthenolide in a xenograft hormone refractory prostate
Rajasubramaniam Shanmugam1, Vetrichelvan Jayaprakasan, Yesim Gokmen-Polar
1Department of Medicine, Indiana University, Indianapolis, Indiana, USA.
Background:
Nuclear Factor kappa B (NFkappaB) 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 NFkappaB-DNA binding. Parthenolide downregulated anti-apoptotic genes under NFkappaB 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.
Insights
Parthenolide inhibits cancer cell growth and angiogenesis by blocking NFkappaB signaling. This natural compound enhances chemotherapy and hormonal therapy effectiveness in preclinical models.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Nuclear Factor kappa B (NFkappaB) is constitutively active in human cancers.
- Parthenolide (P), a natural sesquiterpene lactone, inhibits NFkappaB.
- NFkappaB plays a critical role in cancer progression and survival.
Purpose of the Study:
- To investigate the anti-tumor and anti-angiogenic effects of parthenolide.
- To assess parthenolide's potential to enhance chemotherapy and hormonal therapy.
- To elucidate the molecular mechanisms underlying parthenolide's activity.
Main Methods:
- In vitro studies using CWR22Rv1 and HUVEC cell lines.
- In vivo studies using a CWR22Rv1 xenograft mouse model.
- Assessed cell proliferation, apoptosis, NFkappaB-DNA binding, gene expression, and therapeutic efficacy.
Main Results:
- Parthenolide inhibited proliferation and induced apoptosis in cancer and endothelial cells.
- Parthenolide abrogated NFkappaB-DNA binding and downregulated NFkappaB-regulated anti-apoptotic genes.
- Parthenolide augmented the in vivo efficacy of docetaxel and restored sensitivity to bicalutamide.
Conclusions:
- Parthenolide exhibits significant anti-tumor and anti-angiogenic activity.
- Parthenolide demonstrates potential as an adjuvant therapy to enhance chemotherapy and hormonal therapy.
- Parthenolide's mechanism involves inhibition of NFkappaB signaling and activation of JNK.
