Histamine H1 receptor antagonists selectively kill cisplatin-resistant human cancer cells

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 resistan...

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Autores principales:	Nobuki Matsumoto, Miku Ebihara, Shiori Oishi, Yuku Fujimoto, Tomoko Okada, Toru Imamura
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/911c5b64f856425d9341c0446eb9ffee
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spelling	oai:doaj.org-article:911c5b64f856425d9341c0446eb9ffee2021-12-02T15:23:02ZHistamine H1 receptor antagonists selectively kill cisplatin-resistant human cancer cells10.1038/s41598-021-81077-y2045-2322https://doaj.org/article/911c5b64f856425d9341c0446eb9ffee2021-01-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-81077-yhttps://doaj.org/toc/2045-2322Abstract 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.Nobuki MatsumotoMiku EbiharaShiori OishiYuku FujimotoTomoko OkadaToru ImamuraNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-16 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Nobuki Matsumoto Miku Ebihara Shiori Oishi Yuku Fujimoto Tomoko Okada Toru Imamura Histamine H1 receptor antagonists selectively kill cisplatin-resistant human cancer cells
description	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.
format	article
author	Nobuki Matsumoto Miku Ebihara Shiori Oishi Yuku Fujimoto Tomoko Okada Toru Imamura
author_facet	Nobuki Matsumoto Miku Ebihara Shiori Oishi Yuku Fujimoto Tomoko Okada Toru Imamura
author_sort	Nobuki Matsumoto
title	Histamine H1 receptor antagonists selectively kill cisplatin-resistant human cancer cells
title_short	Histamine H1 receptor antagonists selectively kill cisplatin-resistant human cancer cells
title_full	Histamine H1 receptor antagonists selectively kill cisplatin-resistant human cancer cells
title_fullStr	Histamine H1 receptor antagonists selectively kill cisplatin-resistant human cancer cells
title_full_unstemmed	Histamine H1 receptor antagonists selectively kill cisplatin-resistant human cancer cells
title_sort	histamine h1 receptor antagonists selectively kill cisplatin-resistant human cancer cells
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/911c5b64f856425d9341c0446eb9ffee
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Histamine H1 receptor antagonists selectively kill cisplatin-resistant human cancer cells

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