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

Nobuki Matsumoto1, Miku Ebihara2, Shiori Oishi2

  • 1Cell Regulation Laboratory, Bionics Program, Tokyo University of Technology Graduate School of Bionics, Computer and Media Science, Hachioji, Japan.

Scientific Reports
|January 16, 2021
PubMed

Insights

Histamine H1 receptor antagonists, like cloperastine, selectively kill cisplatin-resistant cancer cells. This targeted cell death is linked to fibroblast growth factor 13 (FGF13) expression, offering new therapeutic strategies.

Area of Science:

  • Oncology
  • Pharmacology
  • Molecular Biology

Background:

  • Cancer drug resistance, particularly to cisplatin, is a significant clinical challenge.
  • Fibroblast growth factor 13 (FGF13) upregulation is implicated in cisplatin resistance in cervical cancer (HeLa cisR) and poor patient prognosis.
  • Understanding the mechanisms of drug resistance is crucial for developing effective cancer therapies.

Purpose of the Study:

  • To investigate the efficacy of histamine receptor antagonists against cisplatin-resistant cancer cells.
  • To elucidate the role of fibroblast growth factor 13 (FGF13) in mediating sensitivity to these antagonists.
  • To explore novel therapeutic strategies for overcoming cisplatin resistance in cancer.

Main Methods:

  • Treatment of cisplatin-resistant cancer cell lines (HeLa cisR, A549 cisR) with cloperastine and other histamine receptor antagonists.
  • Gene knockdown of fibroblast growth factor 13 (FGF13) in resistant cells.
  • Assessment of cell viability and cytotoxicity across different cell lines and treatment conditions.

Main Results:

  • Cloperastine and related histamine H1 receptor antagonists selectively killed cisplatin-resistant HeLa cisR and A549 cisR cells.
  • The selective cytotoxicity was dependent on fibroblast growth factor 13 (FGF13) expression, as knockdown abolished sensitivity.
  • Other histamine receptor antagonists (H2, H3, H4) showed minimal or no cytotoxicity against these resistant cells.

Conclusions:

  • Histamine H1 receptor antagonists demonstrate selective killing of cisplatin-resistant cancer cells.
  • This effect is mediated by a mechanism involving autocrine histamine activity and high FGF13 expression.
  • H1 receptor antagonists represent a potential adjunct therapy for drug-resistant cancers, possibly in combination with existing anticancer agents.

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