Exploration of MDM2-AURKB Regulatory Interaction: Implications for Cell Cycle Arrest and Cell Death in Lung Cancer
Abstract
Lung cancer is the most prevalent cause of cancer-related deaths worldwide, with a 5-year survival rate of 26.6% in the USA contributing to a higher mortality in comparison to other cancers. Among various abnormalities, MDM2 overexpression can positively influence the intracellular mechanisms and contribute to cancer progression through AURKB activation. Also, FOXO3A, a member of the Forkhead Box transcription factors linked to MDM2, serve as intermediates for various cellular mechanisms, including tumorigenesis, cell cycle progression, DNA damage, and cell death. Therefore, blocking MDM2 with specific inhibitors has become one of the promising strategies for the restoration of p53 mediated tumor suppressor function that is effective for the treatment of a wide range of cancers. The main objective of this study was to understand the mechanisms linking MDM2 and AURKB by using RG7388, CM272, and SAHA treatments in A549 and H460 lung cancer cells. The effects of individual treatment of these drugs on cell cycle arrest and cell death mechanisms were analyzed using the in vitro experimental model. Induction of cell cycle arrest by RG7388 in cancer cells was evidenced by elevated p53, p21, and p27 expression levels, and appears to induce cell death also in a p21-dependent manner. However, more studies are required to fully understand the effects of CM272 and SAHA in disrupting the link between MDM2 and AURKB (This project was supported by the PFRDG Grant of Nova Southeastern University and by the generous support from the Royal Dames of Cancer Research Ft. Lauderdale, FL).
Faculty Sponsors
Dr. Katie Crump, Dr. Umamaheswari Natarajan, Dr. Appu Rathinavelu
Project Type
Event
Location
Alvin Sherman Library
Start Date
4-3-2024 12:30 PM
End Date
4-4-2024 1:30 PM
Exploration of MDM2-AURKB Regulatory Interaction: Implications for Cell Cycle Arrest and Cell Death in Lung Cancer
Alvin Sherman Library
Lung cancer is the most prevalent cause of cancer-related deaths worldwide, with a 5-year survival rate of 26.6% in the USA contributing to a higher mortality in comparison to other cancers. Among various abnormalities, MDM2 overexpression can positively influence the intracellular mechanisms and contribute to cancer progression through AURKB activation. Also, FOXO3A, a member of the Forkhead Box transcription factors linked to MDM2, serve as intermediates for various cellular mechanisms, including tumorigenesis, cell cycle progression, DNA damage, and cell death. Therefore, blocking MDM2 with specific inhibitors has become one of the promising strategies for the restoration of p53 mediated tumor suppressor function that is effective for the treatment of a wide range of cancers. The main objective of this study was to understand the mechanisms linking MDM2 and AURKB by using RG7388, CM272, and SAHA treatments in A549 and H460 lung cancer cells. The effects of individual treatment of these drugs on cell cycle arrest and cell death mechanisms were analyzed using the in vitro experimental model. Induction of cell cycle arrest by RG7388 in cancer cells was evidenced by elevated p53, p21, and p27 expression levels, and appears to induce cell death also in a p21-dependent manner. However, more studies are required to fully understand the effects of CM272 and SAHA in disrupting the link between MDM2 and AURKB (This project was supported by the PFRDG Grant of Nova Southeastern University and by the generous support from the Royal Dames of Cancer Research Ft. Lauderdale, FL).
