**Background**
Pyrimidine nucleosides are essential components of nucleic acids and play critical roles in cellular metabolism and signal transduction. Among these, cytidine serves as a fundamental building block of RNA and acts as a precursor to uridine. Beyond its structural role, cytidine is heavily involved in the regulation of neuronal-glial glutamate cycling, which in turn influences mitochondrial function, catecholamine synthesis, and cerebral phospholipid metabolism. Dysregulation of these pathways is often linked to mood disorders and various malignancies. Given its multifaceted role in maintaining cellular homeostasis and its potential to modulate neurotransmitter levels, cytidine has become a subject of interest in both neuroscience and oncology. In this context, we will introduce a human endogenous metabolite – Cytidine.
**Definition**
Cytidine is a pyrimidine nucleoside that acts as a microbial and human endogenous metabolite. According to the Cytidine description, it serves as a key precursor for uridine and regulates critical metabolic cycles in the brain.
**In Vitro and In Vivo Studies**
The Cytidine biological activity has been extensively evaluated across various biological models. In vivo studies demonstrate that cytidine can decrease glutamate and glutamine levels, which leads to an earlier improvement of depressive symptoms in mood disorder models. Regarding Cytidine cancer research, in vitro assays have shown that the compound exhibits potent inhibitory effects on the growth of several cancer cell lines. Specifically, cytidine demonstrated significant cytotoxicity against the osteosarcoma cell line SK-ES-1 with an IC50 of 0.09 μg/mL, the KHOS-321H osteosarcoma line with an IC50 of 0.27 μg/mL, and the lung adenocarcinoma PC-8 line with an IC50 of 0.28 μg/mL. Additionally, it showed inhibitory activity against the HOS-TE85 osteosarcoma line (IC50 = 2.6 μg/mL), the lung adenocarcinoma PC-9 line (IC50 = 1.6 μg/mL), and the stomach adenocarcinoma MKN-28 line (IC50 = 4.5 μg/mL). However, cytidine showed limited efficacy (IC50 > 100 μg/mL) in other lines, including NUGC-4, OST, PC-13, PC-3, QG-56, ST-KM-1, and SW480. In conclusion, cytidine is a versatile endogenous metabolite with potential applications in treating mood disorders and inhibiting the growth of specific osteosarcoma and adenocarcinoma cell lines.
Keywords
Cytidine, 65-46-3, Cytosine β-D-riboside, Cytosine-1-β-D-ribofuranoside, Nucleoside Antimetabolite/Analog, Endogenous Metabolite, uridine, RNA, nucleoside, ribofuranose, Inhibitor, inhibitor, inhibit
References
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[2] Wurtman RJ, et al. Effect of oral CDP-choline on plasma choline and uridine levels in humans. Biochem Pharmacol. 2000 Oct 1;60(7):989-92.
[3] Machado-Vieira R, et, al. New therapeutic targets for mood disorders. ScientificWorldJournal. 2010 Apr 13;10:713-26.