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Updated: Jan 14, 2026
A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer
Published on: March 6, 2018
Innovative Se-Flutamide Derivatives: Enhanced Activity Toward Androgen Receptor (AR)-Dependent and -Independent
Cristina Morán-Serradilla1, Carmen Sanmartín1, Asif Raza2
1Department of Pharmaceutical Sciences, University of Navarra, Irunlarrea, Spain.
Abstract:
Sixteen novel selenoderivatives of flutamide, which is used for treating androgen receptor (AR)-dependent prostate cancer, were developed. All the Se derivatives displayed promising activity against the NCI-60 human cancer cell line panel, which also includes two AR-independent prostate cancer cell lines, DU-145 and PC-3. Conversely to flutamide, compounds a2, a5, and b4 exhibited a potent antiproliferative effect toward AR-dependent LNCaP cells. Several cell death inhibitors were used to determine the underlying regulated cell death processes of a5. Regarding its mechanism of action in these cells, this compound promoted apoptosis by activating both intrinsic and extrinsic apoptotic pathways, without generating reactive oxygen species (ROS). Besides, it induced the G0/G1 cell cycle arrest. Altogether, it could be concluded that this Se-flutamide analog could be a feasible and promising candidate for further development for the treatment of both AR-dependent and -independent prostate cancers.
Insights
New selenium-based flutamide analogs show potent anti-cancer activity. These compounds effectively treat both androgen receptor (AR)-dependent and -independent prostate cancers by inducing apoptosis and cell cycle arrest.
Area of Science:
- Medicinal Chemistry
- Oncology
- Molecular Biology
Background:
- Flutamide is a key treatment for androgen receptor (AR)-dependent prostate cancer.
- Developing novel therapeutics for AR-independent prostate cancer remains a critical challenge.
- Exploring selenoderivatives offers a promising avenue for enhanced anti-cancer efficacy.
Purpose of the Study:
- To synthesize and evaluate novel selenoderivatives of flutamide.
- To assess the antiproliferative activity of these compounds against a panel of human cancer cell lines, including AR-dependent and AR-independent prostate cancer models.
- To elucidate the mechanism of action for promising candidates.
Main Methods:
- Synthesis of sixteen novel selenoderivatives of flutamide.
- In vitro screening against the NCI-60 human cancer cell line panel.
- Assessment of antiproliferative effects on LNCaP, DU-145, and PC-3 prostate cancer cell lines.
- Apoptosis and cell cycle analysis using cell death inhibitors and flow cytometry.
Main Results:
- All synthesized selenoderivatives demonstrated promising activity against the NCI-60 panel.
- Compounds a2, a5, and b4 showed potent antiproliferative effects against AR-dependent LNCaP cells, unlike flutamide.
- Compound a5 induced apoptosis via intrinsic and extrinsic pathways, arrested cells in G0/G1 phase, and did not generate reactive oxygen species (ROS).
Conclusions:
- The novel Se-flutamide analogs exhibit significant potential for treating both AR-dependent and AR-independent prostate cancers.
- Compound a5 represents a promising candidate for further preclinical and clinical development.
- This research opens new therapeutic strategies for advanced prostate cancer treatment.
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