TY - JOUR AU - Balkhi, Shayan AU - Saghaeian Jazi, Marie AU - Mansour Samaei, Nader AU - Rezaie, Nahid AU - Farahmandrad, Mahtab PY - 2025 DA - 2025/07/07 TI - Serum Shock Enhances Endogenous Melatonin Production and Mitochondrial Gene Regulation in U87-MG Glioblastoma Cells JO - OBM Genetics SP - 301 VL - 09 IS - 03 AB - Glioblastoma (GBM) is the most aggressive primary brain tumor, with a poor prognosis despite advancements in understanding its biology. Melatonin, a key regulator of metabolism and cellular homeostasis, is known for its neuroprotective and anti-cancer properties. While traditionally linked to pineal gland secretion, emerging evidence suggests that glioblastoma cells can produce melatonin within their mitochondria. This study investigates whether serum shock can influence endogenous melatonin production and mitochondrial gene expression in glioblastoma cells (U87-MG). U87-MG cells were subjected to serum shock (50% horse serum for 2 hours, followed by serum-free conditions for 8 hours). Melatonin levels in cell supernatants and lysates were quantified using ELISA, while cell proliferation was assessed via BrdU staining and flow cytometry. Additionally, qRT-PCR was used to analyze the expression of key mitochondrial and circadian genes (TFAM, BMAL1, PPARGC1A, and DNM1L). Our findings reveal a significant increase in both intracellular and extracellular melatonin levels in serum-shocked cells compared to controls (p < 0.0003). Notably, TFAM (Transcription Factor A, Mitochondrial), PPARGC1A (Peroxisome Proliferative Activated Receptor, Gamma, Coactivator 1), BMAL1 (Basic Helix-Loop-Helix ARNT-like 1), and DNM1L (dynamin 1 like) expression levels were significantly upregulated (p < 0.0002), suggesting enhanced mitochondrial activity and circadian regulation. Although serum shock slightly increased the proliferation rate of U87-MG cells, the effect was not statistically significant. These results indicate that serum shock triggers metabolic adaptation in glioblastoma cells, leading to increased endogenous melatonin production and enhanced mitochondrial gene expression. This study highlights the potential role of intrinsic melatonin in glioblastoma metabolism, warranting further research into its implications for tumor progression and therapeutic strategies. SN - 2577-5790 UR - https://doi.org/10.21926/obm.genet.2503301 DO - 10.21926/obm.genet.2503301 ID - Balkhi2025 ER -