Induction of Necroptosis in MCF-7 Breast Cancer Cells Through Caspase-Independent Mechanisms Following SAHA Treatment
Abstract
Currently, many anti-cancer drugs are known to induce programmed cell death (apoptosis) through activation of intrinsic or extrinsic pathways. However, many types of cancer cells have acquired resistance to apoptosis-mediated cell death. Therefore, simultaneous induction of other forms of cell death in addition to apoptosis of cancer cells is becoming an attractive strategy. For this purpose, we initially explored the role of XIAP in caspase-dependent and caspase-independent mechanisms of cell death. Our western blot data revealed that RIPK3 and MLKL levels were significantly elevated in MCF-7 cells following SAHA treatment. During induction of SAHA-induced cell death, the XIAP levels were also found to be elevated in MCF-7 cells. Based on our experimental results, we are able to demonstrate that treatment with HDAC inhibitor SAHA induced cell death through RIPK3 and MLKL mediated necroptosis pathway in MCF-7 cells. Our results suggest that MCF-7 cells maybe switching to necroptosis mediate the cell death pathway due to the inhibition of caspases by increased levels of XIAP. Upregulation of XIAP has been previously reported to suppress apoptosis by blocking caspase-mediated cascade. So far, our results have suggested that SAHA could induce necroptosis in MCF-7 breast cancer cells through the elevation of XIAP, RIPK3, and MLKL. (Research supported by the Royal Dames of Cancer Research Inc. Ft. Lauderdale FL)
Faculty Sponsors
Dr. Umamaheswari Natarajan, Dr. Thiagarajan Venkatesan, Dr. Appu Rathinavelu
Project Type
Event
Location
Alvin Sherman Library
Start Date
4-6-2022 12:00 PM
End Date
4-7-2022 5:00 PM
Induction of Necroptosis in MCF-7 Breast Cancer Cells Through Caspase-Independent Mechanisms Following SAHA Treatment
Alvin Sherman Library
Currently, many anti-cancer drugs are known to induce programmed cell death (apoptosis) through activation of intrinsic or extrinsic pathways. However, many types of cancer cells have acquired resistance to apoptosis-mediated cell death. Therefore, simultaneous induction of other forms of cell death in addition to apoptosis of cancer cells is becoming an attractive strategy. For this purpose, we initially explored the role of XIAP in caspase-dependent and caspase-independent mechanisms of cell death. Our western blot data revealed that RIPK3 and MLKL levels were significantly elevated in MCF-7 cells following SAHA treatment. During induction of SAHA-induced cell death, the XIAP levels were also found to be elevated in MCF-7 cells. Based on our experimental results, we are able to demonstrate that treatment with HDAC inhibitor SAHA induced cell death through RIPK3 and MLKL mediated necroptosis pathway in MCF-7 cells. Our results suggest that MCF-7 cells maybe switching to necroptosis mediate the cell death pathway due to the inhibition of caspases by increased levels of XIAP. Upregulation of XIAP has been previously reported to suppress apoptosis by blocking caspase-mediated cascade. So far, our results have suggested that SAHA could induce necroptosis in MCF-7 breast cancer cells through the elevation of XIAP, RIPK3, and MLKL. (Research supported by the Royal Dames of Cancer Research Inc. Ft. Lauderdale FL)
