Tracking Metabolic Responses to Citalopram in Colon Cells with Raman Spectroscopy

The antidepressant citalopram, primarily known for its selective serotonin reuptake inhibitor properties, has attracted interest in the broader scope of its effects on cellular metabolism beyond the brain. This study explores metabolic alterations induced by citalopram in human colon cells, both normal and cancerous. Understanding the fate of citalopram in the colon environment is crucial for assessing its systemic and localized effects, particularly in the context of the colon-brain axis and metabolic reprogramming observed in cancer cells. We review the impact of citalopram on metabolic pathways, its transformation in colon cells, and differences between normal and cancerous cells in handling this compound. This study demonstrates that citalopram induces metabolic alterations in cancerous Caco-2 (G1), LoVo (G4), and normal CCD-18Co colon cells. Using Raman spectroscopy and imaging, distinct biochemical changes were identified in the endoplasmic reticulum and lipid droplets after treatment. These changes were reflected in Raman band intensity ratios 1080/1292 cm^-1, 1004/1660 cm^-1, and 1444/1266 cm^-1. Citalopram treatment led to altered lipid ratios (I_1444/1266) and increased nucleic acid (I_1080/1292) and protein (I_1004/1660) ratios, especially in cancerous cells, suggesting modulated lipogenesis, altered transcriptional activity, and endoplasmic reticulum stress-related protein changes. Raman spectroscopy proved to be a label-free method for monitoring drug-induced metabolic responses at the subcellular level. Citalopram also significantly reduced endoplasmic reticulum and lipid droplet areas in Caco-2 and LoVo cells, indicating disrupted cellular homeostasis and increased sensitivity to toxin-induced stress. In contrast, normal CCD-18Co fibroblasts showed increased lipid droplet accumulation, suggesting an adaptive detoxification response.