RRC ID 63630
Author Matsumoto N, Ebihara M, Oishi S, Fujimoto Y, Okada T, Imamura T.
Title Histamine H1 receptor antagonists selectively kill cisplatin-resistant human cancer cells.
Journal Sci Rep
Abstract Cancer therapy is often hampered by the disease's development of resistance to anticancer drugs. We previously showed that the autonomously upregulated product of fibroblast growth factor 13 gene (FGF13; also known as FGF homologous factor 2 (FHF2)) is responsible for the cisplatin resistance of HeLa cisR cells and that it is likely responsible for the poor prognosis of cervical cancer patients treated with cisplatin. Here we show that cloperastine and two other histamine H1 receptor antagonists selectively kill HeLa cisR cells at concentrations that little affect parental HeLa S cells. The sensitivity of HeLa cisR cells to cloperastine was abolished by knocking down FGF13 expression. Cisplatin-resistant A549 cisR cells were similarly susceptible to cloperastine. H2, H3, and H4 receptor antagonists showed less or no cytotoxicity toward HeLa cisR or A549 cisR cells. These results indicate that histamine H1 receptor antagonists selectively kill cisplatin-resistant human cancer cells and suggest that this effect is exerted through a molecular mechanism involving autocrine histamine activity and high-level expression of FGF13. We think this represents a potential opportunity to utilize H1 receptor antagonists in combination with anticancer agents to treat cancers in which emergent drug-resistance is preventing effective treatment.
Volume 11(1)
Pages 1492
Published 2021-1-15
DOI 10.1038/s41598-021-81077-y
PII 10.1038/s41598-021-81077-y
PMID 33452347
PMC PMC7810706
MeSH Apoptosis / drug effects Cell Line, Tumor Cisplatin / pharmacology Drug Resistance, Neoplasm / physiology* Fibroblast Growth Factors / genetics Fibroblast Growth Factors / metabolism Gene Expression / genetics Gene Expression Regulation, Neoplastic / drug effects HeLa Cells Histamine / pharmacology Histamine H1 Antagonists / metabolism Histamine H1 Antagonists / pharmacology* Histamine H2 Antagonists / pharmacology Humans Neoplasms / drug therapy Neoplasms / metabolism* Piperidines / pharmacology Receptors, Histamine H1 / genetics Receptors, Histamine H1 / metabolism
IF 3.998
Human and Animal Cells A549(RCB0098)