Abstract 6784: Effect of novel gold(I) compounds on cell proliferation and signaling protein expression in MDA-MB-231 breast cancer cells

Abstract Gold(I) compounds have been gaining prominence in research as alternative metallo-chemotherapeutic strategies against chemo-resistant tumors. However, the cellular and molecular mechanisms by which gold(I) compounds disrupt cellular processes critical to breast cancer cell proliferation are largely unknown. Our study evaluated the effect of eight novel gold(I) chloride compounds (Table 1) on MDA-MB-231 breast cancer cell proliferation and their mechanistic action on signaling proteins (Bax, Bcl2, pERK1/2). Cell proliferation was assessed by the MTT assay for 24 to 72 hours, and protein expression was analyzed by western blotting and immunodetection after exposure to gold(I) chloride compounds at their respective IC50 concentrations. Our results indicate that except for PEt3AuCl, all compounds inhibited cell proliferation across all exposure times. PCy3AuCl, PiPr3AuCl, PPh3AuCl and PMe3AuCl exhibited the greatest efficacy at low micromolar doses. PPh3AuCl (2-fold) and PBu3AuCl (2.5-fold) displayed high Bax/Bcl2 ratios suggesting proapoptotic effects. All other compounds showed either decreased or unaltered Bax/Bcl2 ratios. Each compound inhibited pERK1/2, with PiPr3AuCl (70%), PMe3AuCl (64%), and PCy3AuCl (52%) showing the greatest inhibition. Overall, our results suggest PCy3AuCl, PiPr3AuCl, and PMe3AuCl inhibited cell proliferation at low micromolar doses most effectively in MDA-MB-231 cells and the cellular mechanism of action likely varies by compound. These could be through altered status of the cell proliferative pERK1/2 protein and/or the apoptotic proteins Bax or Bcl2 in this cell line. This study provides new insights into the cellular mechanism by which these gold(I) compounds may exert their effects in this triple negative human breast cancer cell line and contributes to the growing evidence supporting the potential of gold(I) compounds in cancer therapeutics. Table 1 Effect of Gold(I) Compounds on Cell Proliferation Gold(I) Compound Name Concentration Range Tested (μM) 48 Hour IC50 (μM) Proliferation Inhibition (48 hours) (%) PMe3AuCl 0.1 - 7.5 0.94 ± 0.19 15.8 - 88.4 PEt3AuCl 1 - 300 - 0 - 1.9 PiPr3AuCl 0.1 - 7.5 0.56 ± 0.36 7 - 99.2 PBu3AuCl 0.01 - 2.5 6.3 ± 0.39 0 - 45.7 PtBu3AuCl 0.1 - 7.5 2.3 ± 1.2 0 - 98.6 (PTA)AuCl 1 - 100 69 ± 0.78 0 - 68.3 PCy3AuCl 0.1 - 7.5 0.37 ± 0.21 16.3 - 98.6 PPh3AuCl 1 - 15 1.78 ± 0.40 15.4 - 99.5 Citation Format: Alexis Pawlak, Talitha T. Rajah. Effect of novel gold(I) compounds on cell proliferation and signaling protein expression in MDA-MB-231 breast cancer 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 6784.