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Updated: May 15, 2026
A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer
Published on: March 6, 2018
Ursolic acid sensitizes prostate cancer cells to TRAIL-mediated apoptosis
Seoung Woo Shin1, Jeen-Woo Park
1School of Life Sciences and Biotechnology, College of Natural Sciences, Kyungpook National University, Taegu 702-701, Korea.
Abstract:
Prostate cancer is one of the most commonly occurring malignancies in men, and because existing treatments are not able to manage this neoplasm adequately, novel approaches are needed. Although tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has strong antitumor activity via the induction of apoptotic cell death in a wide range of tumor cell types and has negligible toxicity to most normal cells, some prostate carcinoma cells are resistant to the apoptotic effects of TRAIL. Therefore, combinatorial approaches with TRAIL and different chemotherapeutic agents have been developed to overcome the resistance of cancer cells to TRAIL. Here, we investigated the sensitizing effects of ursolic acid (UA), a pentacyclic triterpenoid found in many plants, on TRAIL-induced prostate cancer cell apoptosis. We found TRAIL-induced prostate cancer cells apoptosis was significantly enhanced by UA, and that UA induced CHOP-dependent DR5 up-regulation. This study shows the use of UA as a sensitizer for TRAIL-induced apoptotic cell death offers a promising means of enhancing the efficacy of TRAIL-based prostate cancer treatments.
Insights
Ursolic acid (UA) enhances the effectiveness of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) in killing prostate cancer cells. This combination therapy shows promise for improving prostate cancer treatment outcomes.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Prostate cancer is a prevalent malignancy in men requiring novel treatment strategies.
- Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) exhibits potent anti-cancer effects but faces resistance in some prostate cancer cells.
- Combinatorial therapies are being explored to overcome TRAIL resistance in cancer treatment.
Purpose of the Study:
- To investigate the sensitizing effect of ursolic acid (UA) on TRAIL-induced apoptosis in prostate cancer cells.
- To elucidate the molecular mechanisms underlying UA's sensitization of TRAIL-induced apoptosis.
Main Methods:
- Treatment of prostate cancer cells with TRAIL and varying concentrations of UA.
- Assessment of apoptosis induction using cell viability assays.
- Analysis of key protein expression, including DR5 and CHOP, via Western blotting.
Main Results:
- Ursolic acid significantly enhanced TRAIL-induced apoptosis in prostate cancer cells.
- UA treatment led to the up-regulation of DR5 expression in a CHOP-dependent manner.
- The combination of UA and TRAIL demonstrated a synergistic effect on cancer cell death.
Conclusions:
- Ursolic acid acts as a sensitizer, potentiating TRAIL-induced apoptosis in prostate cancer.
- UA-mediated sensitization involves the induction of CHOP and subsequent DR5 up-regulation.
- UA represents a promising adjuvant agent for enhancing the efficacy of TRAIL-based prostate cancer therapies.
