Preface
The long-awaited 39th Annual Meeting of the European Urological Association (EAU24) in 2024 was held in Paris, France from April 5 to 8 local time. As the largest and most influential urology conference in Europe, EAU24 has an extraordinary impact on the international urology community. This event not only attracted urology experts and scholars from all over the world, but also brought together the latest research results and cutting-edge technologies in the field of urology, injecting new vitality into the development of the field of urology. During the conference, two basic studies from Sun Yat-sen Memorial Hospital of Sun Yat-sen University and West China Hospital of Sichuan University explored the potential role of melatonin in inhibiting the progression of prostate cancer.
P162: Melatonin inhibits prostate cancer progression by inducing P53 phosphorylation enhances SLC7A11-mediated ferroptosis
1. Background
Given the high incidence of prostate cancer (PCa) and limited treatment options, novel therapeutic strategies targeting specific molecular pathways are imperative. This study explores the therapeutic potential of melatonin for PCa. Melatonin intervention can induce phosphorylation of P53 and activate SLC7A11, and SLC7A11 is a key regulator of iron homeostasis in cells and is involved in ferroptosis. Melatonin upregulates SLC7A11 promotes iron-dependent death of PCa cells. In addition, the melatonization intervention significantly inhibited PCa cell proliferation, migration, and invasion, and induced cell cycle arrest. These effects coincide with increased expression of ferroptosis markers and decreased levels of the anti-apoptotic protein Bcl-2.
2. Research methods
To detect the effects of the melatonin intervention, the research team performed Western blot analysis to assess the expression of P53 phosphorylation, SLC7A11 and ferroptosis markers, as well as Bcl-2 protein levels. Immunofluorescence staining was used to observe the localization and expression of SLC7A11 in melatonin-assisted PCa cells. The effect of melatonin on PCa cell viability is assessed using a cell viability assay. The migration and invasion ability of PCa cells were assessed by Transwell migration/invasion assays. In addition, flow cytometry was used to analyze the cell cycle distribution of melatonin-treated PCa cells.
3 Research results
The results of this study showed that melatonin intervention could induce phosphorylation of P53 in PCa cells, thereby activating the P53 pathway. This activation leads to upregulation of SLC7A11 expression, SLC7A11 a key regulator of cellular iron homeostasis and an important mediator of ferroptosis. In PCa cells, melatonin-induced SLC7A11 upregulation enhances iron-dependent cell death through ferroptosis.
4. Conclusions of the study
In summary, melatonin may be a promising drug candidate for the development of PCa-targeted therapies. By inducing P53 phosphorylation, activating SLC7A11, and promoting ferroptosis, melatonin offers a novel method to inhibit the progression of PCa. Further research and clinical investigations are needed in order to translate the results of these promising in vitro studies into effective treatments for PCa patients.
A0546: Melatonin inhibits the growth and metastasis of PCa by promoting NRF2-mediated ferroptosis by increasing the liquid-liquid phase separation behavior of androgen receptors
1. Background
There is a lack of effective treatment for advanced PCa, which is often accompanied by elevated androgen receptor (AR) expression. Melatonin (MEL) is a multifunctional indoleamine molecule that inhibits proliferation of prostate cancer cells, but its specific mechanism of action is unknown.
2. Research methods
The role of MEL in PCa was studied in vitro and in vivo, and its possible mechanism of action was explored through transcriptome sequencing, co-immunoprecipitation (Co-IP), gene overexpression and gene knockout experiments.
3 Research results
MEL inhibits the proliferation and metastasis of 22Rv1 and C4-2B cells and reverses the resistance of PCa cells to enzalutamide. In vivo experiments showed that intraperitoneal injection of MEL significantly inhibited the growth of subcutaneous xenografts and prolonged the survival time of mice. In terms of mechanism, it was found that MEL intervention was beneficial to the liquid-liquid phase separation (LLP) behavior of AR, and the activated AR could form transcriptionally active condensates, and the protein level was significantly upregulated. Activated AR inhibits Gpx4 expression by decreasing phosphorylation of Nrf2, thereby promoting ferroptosis of PCa. In addition, activated AR decreases the expression of the MCM family (MCM2-10), inhibits the cell cycle, and inhibits cell proliferation.
4. Conclusions of the study
The results of this study suggest the application prospect of MEL in the treatment of PCa and provide new ideas for the treatment of advanced PCa.
Resources:
[1] https://urosource.uroweb.org/resource-centres/EAU24/257419/abstract
[2] https://urosource.uroweb.org/resource-centres/EAU24/257645/abstract
编辑:Gardenia审校:Gardenia执行:Gardenia
This platform aims to deliver more medical information to healthcare professionals. The content published on this platform should not be used as a substitute for professional medical guidance in any way, nor should it be regarded as diagnosis and treatment advice. If such information is used for purposes other than understanding medical information, the platform does not assume relevant responsibilities. This platform does not mean that it agrees with its descriptions and views on the published content. If copyright issues are involved, please contact us, and we will deal with it as soon as possible.
Yimaitong is a professional online doctor platform, and the mission of the platform is to "sense the pulse of the world's medicine and help China's clinical decision-making". Yimaitong has a series of products such as "Clinical Guidelines", "Medication Reference", "Medical Literature King", "Yizhiyuan", "eYantong" and "ePulse", which fully meet the needs of medical workers in clinical decision-making, obtaining new knowledge and improving scientific research efficiency.