All-trans-retinal as a modulator of metabolic and mitochondrial signatures in non-tumorigenic and malignant breast...

Retinoids are well recognized for their therapeutic potential in pharmacy and medicine. Although extensively studied for their anticancer properties, the specific effects of all-trans-retinal (ALTR) on the metabolism of breast cancer cells-particularly in relation to dose, incubation time, and tumour aggressiveness-remain insufficiently understood. In this study, the metabolic impact of ALTR on non-tumorigenic (MCF10A) and malignant breast cell lines (MCF7, MDA-MB-231) using Raman imaging and biological viability assays (XTT) were examined. Cells were incubated with 1 and 10 µM concentrations of ALTR for 24 and 48 h. Raman spectroscopy and imaging enabled both qualitative and quantitative detection of cellular organelles, allowing us to track ALTR-associated metabolic changes at the subcellular level. Our findings demonstrate that ALTR significantly reduced cell viability, particularly in cancerous lines, while promoting cellular development in non-tumorigenic MCF10A cells. Notably, a Raman band at 1597 cm^-1 appeared in MCF10A cells following ALTR treatment, potentially indicating metabolic conversion of ALTR into esterified forms. Furthermore, ALTR supplementation modulated the redox state of mitochondrial cytochrome c, as reflected by intensity changes in the 1583 cm^-1 band corresponding to its reduced form. These effects were most prominent in non-tumorigenic cells, suggesting enhanced sensitivity to ALTR-induced redox alterations. Collectively, our results highlight the value of Raman spectroscopy and imaging as powerful tools for cancer cell phenotyping and metabolic assessment. The observed inhibition of cancer cell proliferation, combined with alterations in mitochondrial redox balance, positions ALTR as a promising candidate for breast cancer therapy.