Abstract A32: Exemestane inhibits survival and cell cycle regulators and retards AML cell proliferation

Abstract

Abstract Acute myeloid leukemia (AML) is the most common type of leukemia with poor prognosis. Although estrogen plays important roles in female cancers, the recent reports indicate that estrogen and its receptors also attribute to the development of non-gender cancers and AML is one of those. Therefore, the inhibition of estrogen production becomes a potential strategy for AML treatment. Exemestane is an aromatase inhibitor and commonly used for reducing estrogen production in breast cancer patients. Our data showed that Exemestane treatment significantly decreased the proliferation of both KG-1 and HL-60 AML cell lines. Since STAT3 and AKT closely collaborate with estrogen receptor in breast cancer cells, their activations are next to be monitored. In KG-1 cells, the phosphorylations of STAT3 (Y705 and S727) and AKT (S473) were both inhibited by Exemestane treatment. Regarding the cell cycle control, p21 was increased by Exemestane in KG-1 cells in which Cyclin E was reduced. It suggests that CDK2 might be inactivated by Exemestane-reduced Cyclin E and therefore p21 escaped from the CDK2-dependent degradation. Although the signaling findings of Exemestane in KG-1 were interesting, no similar results were found in HL-60 cells except the growth inhibition, suggesting the distinct regulation mechanisms between two cell lines. In summary, these results not only suggest, again, the importance of estrogen demand for AML cells, but also show the novel and potential treatment of AML using blockade of estrogen supply, which could be helpful to uncover novel AML treatments in the future. Citation Format: Mei-chih Chen, Pang-Ting Cheng, Yu-Chiao Cheng, Ho Lin, Chieh-Lin Jerry Teng. Exemestane inhibits survival and cell cycle regulators and retards AML cell proliferation [abstract]. In: Proceedings of the AACR Special Conference: Acute Myeloid Leukemia and Myelodysplastic Syndrome; 2023 Jan 23-25; Austin, TX. Philadelphia (PA): AACR; Blood Cancer Discov 2023;4(3_Suppl):Abstract nr A32.