Presentation Title
Induction of Necroptosis Through Caspase-Independent Mechanisms in Breast Cancer Cells Following HACD Inhibitor Treatment
Presenter Credentials
Grace Waldron, Halmos College of Arts & Sciences and the Guy Harvey Oceanographic Research Center, fourth year undergraduate, Bachelors of Science in Biology
Presenter Degree
BS
College
Halmos College of Arts and Sciences and the Guy Harvey Oceanographic Research Center
Campus Location
Ft. Lauderdale
Format
Poster
IRB Approval Verification
N/A
Abstract
Presently, many anti-cancer treatments are known to induce programmed cell death (apoptosis) by activating intrinsic or extrinsic mechanisms. However, multiple types of cancer cells have developed resistance to apoptosis-mediated cell death.. Therefore, concurrently induction of other forms of cell death mechanisms in addition to apoptosis of cancer cells is becoming a more attractive strategy. For this principle, Initially, we explored the function of XIAP in caspase-dependent and independent cell death mechanisms. Our western blot results showed that the levels of phospho-RIPK3 and MLKL were significantly elevated following Histone deacetylase inhibitors (HDACIs) SAHA treatment in MCF-7 breast cancer cells. In MCF-7 cells, XIAP levels were also found to be increased during induction of SAHA-induced cell death. Based on our results, we are able to demonstrate that treatment with the SAHA induced cell death in MCF-7 cells through the phospho-RIPK3 and MLKL-mediated necroptosis pathway. Our results suggested that MCF-7 cells may switch to necroptosis-mediated cell death due to inhibition of caspases byincreased levels of XIAP. Upregulation of XIAP has been reported to suppress apoptosis by blocking the caspase-depended cascade. So far, our results suggested that SAHA can induce necroptosis in MCF-7 breast cancer cells by increasing the levels of XIAP, phospho-RIPK3, and MLKL expression. (This research was supported by the Royal Dames of Cancer Research Inc. Ft. Lauderdale, FL) References Natarajan, U., Venkatesan, T, Radhakrishnan, V., Samuel, S., Rathinavelu, A. (2018). Differential Mechanisms of Cell Death Induced by HDAC Inhibitor SAHA and MDM2 Inhibitor RG7388 in MCF-7 Cells. Cells Dec 22;8(1):8. doi: 10.3390/cells8010008. Natarajan, U., Venkatesan, T, Radhakrishnan, V., Samuel, S., Rasappan, P., Rathinavelu, A. (2019). Cell Cycle Arrest and Cytotoxic Effects of SAHA and RG7388 Mediated through p21 WAF1/CIP1 and p27 KIP1 in Cancer Cells. Medicina(Kaunas).2019 Jan 29;55(2):30. doi: 10.3390/medicina55020030.
Selection Criteria
1
Induction of Necroptosis Through Caspase-Independent Mechanisms in Breast Cancer Cells Following HACD Inhibitor Treatment
Presently, many anti-cancer treatments are known to induce programmed cell death (apoptosis) by activating intrinsic or extrinsic mechanisms. However, multiple types of cancer cells have developed resistance to apoptosis-mediated cell death.. Therefore, concurrently induction of other forms of cell death mechanisms in addition to apoptosis of cancer cells is becoming a more attractive strategy. For this principle, Initially, we explored the function of XIAP in caspase-dependent and independent cell death mechanisms. Our western blot results showed that the levels of phospho-RIPK3 and MLKL were significantly elevated following Histone deacetylase inhibitors (HDACIs) SAHA treatment in MCF-7 breast cancer cells. In MCF-7 cells, XIAP levels were also found to be increased during induction of SAHA-induced cell death. Based on our results, we are able to demonstrate that treatment with the SAHA induced cell death in MCF-7 cells through the phospho-RIPK3 and MLKL-mediated necroptosis pathway. Our results suggested that MCF-7 cells may switch to necroptosis-mediated cell death due to inhibition of caspases byincreased levels of XIAP. Upregulation of XIAP has been reported to suppress apoptosis by blocking the caspase-depended cascade. So far, our results suggested that SAHA can induce necroptosis in MCF-7 breast cancer cells by increasing the levels of XIAP, phospho-RIPK3, and MLKL expression. (This research was supported by the Royal Dames of Cancer Research Inc. Ft. Lauderdale, FL) References Natarajan, U., Venkatesan, T, Radhakrishnan, V., Samuel, S., Rathinavelu, A. (2018). Differential Mechanisms of Cell Death Induced by HDAC Inhibitor SAHA and MDM2 Inhibitor RG7388 in MCF-7 Cells. Cells Dec 22;8(1):8. doi: 10.3390/cells8010008. Natarajan, U., Venkatesan, T, Radhakrishnan, V., Samuel, S., Rasappan, P., Rathinavelu, A. (2019). Cell Cycle Arrest and Cytotoxic Effects of SAHA and RG7388 Mediated through p21 WAF1/CIP1 and p27 KIP1 in Cancer Cells. Medicina(Kaunas).2019 Jan 29;55(2):30. doi: 10.3390/medicina55020030.