Abstract 4407: Taurine's potential role in tamoxifen resistant MCF-7 cells

Abstract Taurine is a non-proteinogenic amino acid synthesized from cysteine. Although taurine does not contribute to protein synthesis, it regulates glutathione metabolism, upregulates proliferative and anti-oxidative pathways, downregulates pro-apoptotic pathways, and improves mitochondrial function in normal tissues. However, the role of taurine in tumorigenesis and resistance development in cancer, especially breast cancer, is not widely understood. We aim to study metabolic and cellular changes associated with the taurine metabolism pathway in tamoxifen resistant (TAM-R) MCF-7 breast cancer cell lines. Methods: Three TAM-R MCF-7 models were developed using two strategies. The first was achieved by incrementally increasing the dose until reaching a predetermined dose (TAM-P). The second was achieved by taking cell lines from the first method and continuously treating them with 1μM of tamoxifen (TAM-C). NMR was used to quantify the levels of intracellular metabolites, and HPLC/MS-MS was used to calculate taurine uptake by the cells from media. Gene expression levels of ESR1, PI3KCA and PTEN were measured by RT-PCR. GSCA: Gene Set Cancer Analysis platform was used to check the association of a gene set consisting of taurine metabolism pathway genes (CDO1, ADO, GAD1, GAD2, CSAD) with the regulation of cancer related pathways. Results: Taurine, choline, and glutathione concentrations were significantly higher in TAM-C compared to tamoxifen-sensitive control and TAM-P, while cystine was lower in TAM-C. Taurine uptake from the media in TAM-C and control were slightly higher than TAM-P. ESR1 was 40 folds overexpressed in TAM-C and down regulated in TAM-P, while PI3KCA was overexpressed and PTEN was down regulated in both TAM-C and TAM-P. Moreover, there was a positive correlation between taurine metabolism pathway gene set and activation of ER pathway. Conclusion: The significant increase in taurine and decrease in cysteine in the TAM-C group cannot be explained by the marginal increase in taurine uptake alone, which necessities increased synthesis of the taurine. Overexpression of ESR1 in TAM-C could be caused by upregulation of the taurine synthesis pathway. However, overexpression of PI3KCA and down regulation of PTEN indicates reliance on PI3K/AKT/PTEN pathway instead of estrogen signaling pathway. Moreover, increased glutathione and choline concentrations increased antioxidative capacity, mitochondrial function, and resistance to oxidative stress. Citation Format: Yazan I. Hamadneh, Mohammad Alwahsh, Aya Hasan, Ala A. Alhusban, Osama M. Younis, Roland Hergenröder, Lama Hamadneh. Taurine's potential role in tamoxifen resistant MCF-7 cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 4407.