Evaluation of the Effects of MDMX and MDM2 Inhibitors Causing Cell Death in Prostate Cancer Cells
Abstract
Objective: In this research, we examined the molecular mechanisms by which inhibition of the MDM2 and MDMX pathways induces cell death in prostate cancer cells. Background: In the United States alone, more than 3 million men are living with prostate cancer. Though significant advances have been made in treating prostate cancer, the need for new anti-cancer drugs and treatment methods still persists to fight this deadly disease. Therefore, our study explored the intracellular link between MDMX and necroptosis, to determine how manipulating this molecular target can lead to cell cycle arrest and cell death. Methods: The LNCaP Prostate Cancer cells were treated with NSC-207895 and SJ-172550, which are MDMX inhibitors; and RG-7388, which is a potent MDM2 inhibitor. Following drug treatments, the LNCaP cells were lysed and western blot analyses were performed to determine the expression levels of key proteins responsible for cell death through either the necroptosis or apoptosis pathways. Results: The LNCaP cells treated with MDMX inhibitors showed an increase in levels of proteins that promote cell death through necroptosis pathway. However, when the LNCaP cells were treated with the RG-7388, increased levels of apoptotic proteins were detected. Conclusion: Our results indicate that treatment with the MDMX inhibitors primarily activates the necroptotic pathway in LNCaP cells. To further assess the intracellular mechanisms of how NSC-207895, SJ-172550, and RG-7388 treatments induce differential cell death in LNCaP cells, additional experiments will be conducted. Acknowledgment: This research study was supported by the Royal Dames of Cancer Research Inc., Ft. Lauderdale, Florida.
Faculty Sponsors
Dr. Umamaheswari Natarajan, Dr. Appu Rathinavelu, Dr. Venkatesh Shanbhag
Project Type
Event
Location
Alvin Sherman Library
Start Date
4-3-2024 12:30 PM
End Date
4-4-2024 1:30 PM
Evaluation of the Effects of MDMX and MDM2 Inhibitors Causing Cell Death in Prostate Cancer Cells
Alvin Sherman Library
Objective: In this research, we examined the molecular mechanisms by which inhibition of the MDM2 and MDMX pathways induces cell death in prostate cancer cells. Background: In the United States alone, more than 3 million men are living with prostate cancer. Though significant advances have been made in treating prostate cancer, the need for new anti-cancer drugs and treatment methods still persists to fight this deadly disease. Therefore, our study explored the intracellular link between MDMX and necroptosis, to determine how manipulating this molecular target can lead to cell cycle arrest and cell death. Methods: The LNCaP Prostate Cancer cells were treated with NSC-207895 and SJ-172550, which are MDMX inhibitors; and RG-7388, which is a potent MDM2 inhibitor. Following drug treatments, the LNCaP cells were lysed and western blot analyses were performed to determine the expression levels of key proteins responsible for cell death through either the necroptosis or apoptosis pathways. Results: The LNCaP cells treated with MDMX inhibitors showed an increase in levels of proteins that promote cell death through necroptosis pathway. However, when the LNCaP cells were treated with the RG-7388, increased levels of apoptotic proteins were detected. Conclusion: Our results indicate that treatment with the MDMX inhibitors primarily activates the necroptotic pathway in LNCaP cells. To further assess the intracellular mechanisms of how NSC-207895, SJ-172550, and RG-7388 treatments induce differential cell death in LNCaP cells, additional experiments will be conducted. Acknowledgment: This research study was supported by the Royal Dames of Cancer Research Inc., Ft. Lauderdale, Florida.
