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Published on: August 2, 2024
Oleuropein Promotes DNA Damage in Prostate Cancer Cells via HIF-1α Downregulation
Hanping Wei1,2, Haoran Wu1,2, Wei Feng1,2
1Department of Urology, Wujin Hospital Affiliated With Jiangsu University, Changzhou, China.
Abstract:
This study aimed to investigate the effects of oleuropein (Ole) on prostate cancer (PCa) cells and its underlying mechanisms, particularly whether it mediates DNA damage through HIF-1α. PCa cells DU145 were treated with different concentrations of Ole (25, 50, 100, 250, and 500 μM) or transfected with HIF-1α overexpression plasmid. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to detect the cell viability; flow cytometry was used to detect apoptosis; quantitative reverse transcription polymerase chain reaction and western blot were employed to measure HIF-1α expression levels. Additionally, comet assay and western blot were employed to evaluate DNA damage and the expression of DNA damage-related proteins (γH2AX and p53). Ole significantly inhibited DU145 cell viability in a concentration-dependent manner (p < 0.01). Additionally, apoptosis rates increased significantly with increasing Ole concentrations (p < 0.01). Ole induced DNA damage in DU145 cells. Notably, overexpression of HIF-1α partially reversed the effects of Ole on PCa cells. Ole inhibits DU145 cell viability, promotes apoptosis, and induces DNA damage, possibly through the HIF-1α pathway. HIF-1α plays a potential role in the anticancer effects of Ole, providing new experimental evidence for its application in PCa research.
Insights
Oleuropein (Ole) inhibits prostate cancer cell viability and promotes apoptosis by inducing DNA damage. This effect is potentially mediated through the Hypoxia-Inducible Factor-1α (HIF-1α) pathway, suggesting Ole
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Prostate cancer (PCa) remains a significant global health concern.
- Identifying novel therapeutic agents and understanding their mechanisms is crucial for effective PCa treatment.
- Oleuropein (Ole), a natural compound, has shown potential anticancer properties.
Purpose of the Study:
- To investigate the effects of Ole on PCa cells (DU145).
- To elucidate the underlying mechanisms, focusing on DNA damage and the role of Hypoxia-Inducible Factor-1α (HIF-1α).
- To evaluate Ole's potential as a therapeutic agent for PCa.
Main Methods:
- Cell viability assessed using MTT assay.
- Apoptosis detected by flow cytometry.
- HIF-1α expression quantified via RT-qPCR and Western blot.
- DNA damage evaluated using comet assay and Western blot for γH2AX and p53.
Main Results:
- Ole significantly inhibited DU145 cell viability in a dose-dependent manner.
- Ole treatment led to a significant increase in apoptosis rates.
- Ole induced DNA damage in PCa cells, evidenced by comet assay and elevated γH2AX/p53 levels.
- Overexpression of HIF-1α partially reversed Ole's inhibitory effects on PCa cells.
Conclusions:
- Ole exhibits significant anticancer effects against PCa cells by inhibiting viability, promoting apoptosis, and inducing DNA damage.
- The Hypoxia-Inducible Factor-1α (HIF-1α) pathway is implicated in mediating Ole's anticancer actions.
- Ole shows promise as a potential therapeutic agent for prostate cancer, warranting further investigation.
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