Palonosetron, a 5-HT3 Receptor Antagonist, Induces G1 Cell Cycle Arrest and Autophagy in Gastric Cancer Cells
Name
ijms-26-10039-v2.pdf
Size
2.74 MB
Format
Adobe PDF
Checksum (MD5)
599305ad60f043bcac11f0eb755f3406
Author(s)
Yoo, Young Chul
Lin, Lin
Lee, Sihak
Shin, Yeeun Rachel
Oh, Ju Eun
Kim, Na Young
Date Issued
October 15, 2025
Journal
International Journal of Molecular Sciences
Publisher
Multidisciplinary Digital Publishing Institute
Citation
Yoo, Y. C., Lin, L., Lee, S., Shin, Y. R., Oh, J. E., & Kim, N. Y. (2025). Palonosetron, a 5-HT3 Receptor Antagonist, Induces G1 Cell Cycle Arrest and Autophagy in Gastric Cancer Cells. International Journal of Molecular Sciences, 26(20), 10039.
Version
Final published version
Abstract
Serotonin or 5-hydroxytryptamine (5-HT) has been implicated in promoting cancer cell growth by acting on 5-HT receptors, such as 5-HT1 and 5-HT2 receptors. However, the role of 5-HT3 receptor antagonists in gastric cancer cell lines remains unclear. This study aimed to evaluate the effect of 5-HT3 receptor antagonists (ondansetron, palonosetron, and ramosetron) on cancer cell growth using AGS and MKN-1 cell lines, as well as the xenograft mouse model. All the three antagonists inhibited cell proliferation, migration, and colony formation in AGS cells. Specifically, palonosetron induced G1 cell cycle arrest, autophagy, and phosphorylation of GSK3β, along with increased expression of p27, p53, and LC3B. In vivo studies demonstrated that palonosetron reduced tumor growth and modulated pro-inflammatory cytokines—tumor necrosis factor alpha, interleukin 6, and interleukin 1β. These findings suggest that 5-HT3 receptor antagonists, especially palonosetron, exert anti-tumor effects in gastric cancer through G1 cell cycle regulation and immunomodulation. The results position palonosetron as a promising lead for further preclinical development in gastric cancer.
MIT Department
Broad Institute of MIT and Harvard
Terms of Use
Creative Commons Attribution
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.3390/ijms262010039
