Investigation of the Effects of Spexin and Phoenixin-14 on Cell Viability and DNA Damage in Glioblastoma and Neuroblastoma Cell Lines
Abstract
Glioblastoma and neuroblastoma are highly aggressive tumors of neural origin, marked by rapid proliferation and limited responsiveness to therapy. A clearer understanding of the molecular factors governing tumor cell growth and survival may facilitate the identification of new biological targets. Increasing evidence suggests that neuropeptides participate in cellular proliferation, metabolism,
and stress adaptation in addition to their established neuroendocrine functions. This study examined whether Spexin and Phoenixin-14 influence viability and DNA integrity in U87-MG glioblastoma and N2a neuroblastoma cells. Cultures were exposed to either peptide at 1, 10, 100 or 1000 nM for 24 h. Metabolic viability was quantified by the MTT reduction assay, whereas DNA damage was characterized through the Comet assay. IC₅₀ estimates and assay outcomes were processed using GraphPad Prism 9. Differences among the groups were examined by one-way ANOVA followed by Tukey’s multiple-comparison procedure, with p < 0.05 considered statistically significant. Spexin lowered U87-MG cell viability at 10, 100 and 1000 nM and N2a cell viability at 1, 100 and 1000 nM. Phoenixin-14 reduced viability only at 1000 nM in U87-MG cells, whereas significant reductions occurred at 10, 100 and 1000 nM in N2a cells. Both peptides increased comet-derived DNA damage indices relative to untreated controls (p < 0.05). These results indicate that Spexin and Phoenixin-14 decreased metabolic cell viability and altered Comet assay parameters associated with DNA damage in U87-MG glioblastoma and N2a neuroblastoma cells, providing preliminary evidence for future investigations of nervous system tumor biology.
Keywords
Spexin, Phoenixin-14, Glioblastoma, Neuroblastoma, Cell viability
References
- Pouyan A, Ghorbanlo M, Eslami M, Jahanshahi M, et al. Glioblastoma multiforme: insights into pathogenesis, key signaling pathways, and therapeutic strategies. Molecular Cancer, 2025; 24(1): 58.
- D’Aprile S, Denaro S, Gervasi A, Vicario N, et al. Targeting metabolic reprogramming in glioblastoma as a new strategy to overcome therapy resistance. Frontiers in Cell and Developmental Biology, 2025; 13: 1535073.
- Del Bufalo F, De Angelis B, Caruana I, Del Baldo G, et al. GD2-CART01 for relapsed or refractory high-risk neuroblastoma. New England Journal of Medicine, 2023; 388(14): 1284-1295.
- Wulf AM, Moreno MM, Paka C, Rampasekova A, et al. Defining pathological activities of ALK in neuroblastoma, a neural crest-derived cancer. International Journal of Molecular Sciences, 2021; 22(21): 11718.
- Becker J, Wilting J. WNT signaling, the development of the sympathoadrenal–paraganglionic system and neuroblastoma. Cellular and Molecular Life Sciences, 2018; 75(6): 1057-1070.
- Zafar A, Wang W, Liu G, Wang X, et al. Molecular targeting therapies for neuroblastoma: progress and challenges. Medicinal Research Reviews, 2021; 41(2): 961-1021.
- Qiu Q-Q, Zhang N, Xu Y-Y, Qin J-W, et al. Melatonin induces autophagy in neuroblastoma by alleviating Pak2-mediated endoplasmic reticulum stress. Molecular Medicine Reports, 2025; 33(2): 74.
- Qiu B, Matthay KK. Advancing therapy for neuroblastoma. Nature reviews Clinical oncology, 2022; 19(8): 515-533.
- Wu Y, Berisha A, Borniger JC. Neuropeptides in cancer: friend and foe? Advanced Biology, 2022; 6(9): 2200111.
- Dong Z, Wang Y, Jin W. The neuroscience of cancer: focus on neuropeptidergic systems. Acta Pharmaceutica Sinica B, 2025; 15(5): 2323-2350.