Name of event: National Conference of
Undergraduate Research (NCUR)
Date of presentation: 04/09/2024
Type of presentation: poster presentation
Title: Identification of novel ACSS2 inhibitors in regulating breast cancer brain metastatic growth
Text of abstract:
Triple negative breast cancer accounts for about 15% of all breast cancers. The overall survival rate of these patients is 77% but drops to 12% once tumors metastasize to the brain which equates to less than 6 months. There are currently no effective drug treatments for patients with brain metastasis, thus there is an urgent need to develop novel treatment strategies. Breast cancer cells that have metastasized to the brain depend on acetate for growth and survival rather than glucose. The acetyl CoA synthetase 2 (ACSS2) enzyme converts acetate to acetyl CoA which is critical for the fatty acid production and gene regulation in tumors in the brain. Our lab has previously shown that genetically targeting ACSS2 can reduce the growth and survival of breast cancer brain metastasis cells in the brain. Further, we have identified novel ACSS2 inhibitor analogs that can cross the blood brain barrier to treat breast cancer brain metastasis. Here, we tested novel secondary analogs of ACSS2 inhibitors for anti-cancer effects using breast cancer brain metastatic (BCBM) cells in vitro and whether they blocked downstream targets of the ACSS2 metabolic pathway. Here, we show that treating BCBM cells with inhibitors 2749, 7033 and 4855 was able to block cell growth measured by crystal violet staining with 4855 having similar effect as first-generation analog 8007. These novel inhibitors were tested further through western blotting and show that novel ACSS2 inhibitor 4855 lead to a reduction in E2F1: a downstream protein of the ACSS2 metabolic pathway. These results suggest a crucial role for ACSS2 in the regulation of breast cancer brain metastasis and identifies ACSS2 inhibitor 4855 as a potent novel ACSS2 inhibitor of BCBM cell growth and supports further testing of these drugs as novel therapeutic agents for the treatment of breast cancer brain metastatic growth.
Date of presentation: 04/09/2024
Type of presentation: poster presentation
Title: Identification of novel ACSS2 inhibitors in regulating breast cancer brain metastatic growth
Text of abstract:
Triple negative breast cancer accounts for about 15% of all breast cancers. The overall survival rate of these patients is 77% but drops to 12% once tumors metastasize to the brain which equates to less than 6 months. There are currently no effective drug treatments for patients with brain metastasis, thus there is an urgent need to develop novel treatment strategies. Breast cancer cells that have metastasized to the brain depend on acetate for growth and survival rather than glucose. The acetyl CoA synthetase 2 (ACSS2) enzyme converts acetate to acetyl CoA which is critical for the fatty acid production and gene regulation in tumors in the brain. Our lab has previously shown that genetically targeting ACSS2 can reduce the growth and survival of breast cancer brain metastasis cells in the brain. Further, we have identified novel ACSS2 inhibitor analogs that can cross the blood brain barrier to treat breast cancer brain metastasis. Here, we tested novel secondary analogs of ACSS2 inhibitors for anti-cancer effects using breast cancer brain metastatic (BCBM) cells in vitro and whether they blocked downstream targets of the ACSS2 metabolic pathway. Here, we show that treating BCBM cells with inhibitors 2749, 7033 and 4855 was able to block cell growth measured by crystal violet staining with 4855 having similar effect as first-generation analog 8007. These novel inhibitors were tested further through western blotting and show that novel ACSS2 inhibitor 4855 lead to a reduction in E2F1: a downstream protein of the ACSS2 metabolic pathway. These results suggest a crucial role for ACSS2 in the regulation of breast cancer brain metastasis and identifies ACSS2 inhibitor 4855 as a potent novel ACSS2 inhibitor of BCBM cell growth and supports further testing of these drugs as novel therapeutic agents for the treatment of breast cancer brain metastatic growth.