Activation of the human TRPA1 channel by different alkylating sulfur and nitrogen mustards and structurally related chemotherapeutic drugs.

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  • Additional Information
    • Source:
      Publisher: Elsevier Country of Publication: Netherlands NLM ID: 7709027 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1879-3169 (Electronic) Linking ISSN: 03784274 NLM ISO Abbreviation: Toxicol Lett Subsets: MEDLINE
    • Publication Information:
      Publication: Amsterdam : Elsevier
      Original Publication: Amsterdam, Elsevier/North Holland.
    • Subject Terms:
      Ifosfamide* ; Nitrogen Mustard Compounds*; Humans ; TRPA1 Cation Channel ; HEK293 Cells ; Alkylating Agents/toxicity ; Nitrogen
    • Abstract:
      An important target in toxicology is the ion channel known as human transient receptor potential ankyrin 1 (hTRPA1). It is triggered by a variety of chemicals, including the alkylating chemical warfare agent sulfur mustard (SM). The activation potentials of structural analogs including O- and sesquimustard, nitrogen mustards (HN1, HN2, and HN3), and related chemotherapeutic drugs (bendamustine, cycylophosphamide, and ifosfamide) were examined in the current study. The aequorin assay was used to measure changes in intracellular calcium levels in human hTRPA1 overexpressing HEK293 cells. The XTT assay was used to determine cytotoxicity. The data presented here highlight that all investigated alkylating substances, with the exception of cyclophosphamide and ifosfamide, cause the activation of hTRPA1. Cytotoxicity and activation of hTRPA1 were found to be related. Compounds with high reactivity had higher cytotoxicity and vice versa. However, inhibiting hTRPA1 with the specific inhibitor AP18 could not reduce the cytotoxicity induced by alkylating agents. As a result, hTRPA1 does not play a significant role in the cytotoxicity of alkylating agents.
      Competing Interests: Declaration of Competing Interest The authors state that they have no financial or personal relationships that may be considered as competing interests.
      (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)
    • Contributed Indexing:
      Keywords: AP18; Bendamustine; Calcium; Chemical warfare agents; O-mustard; Sesquimustard
    • Accession Number:
      0 (TRPA1 Cation Channel)
      UM20QQM95Y (Ifosfamide)
      0 (Nitrogen Mustard Compounds)
      0 (Alkylating Agents)
      N762921K75 (Nitrogen)
      0 (TRPA1 protein, human)
    • Publication Date:
      Date Created: 20230124 Date Completed: 20230215 Latest Revision: 20230215
    • Publication Date:
      20231215
    • Accession Number:
      10.1016/j.toxlet.2023.01.007
    • Accession Number:
      36693442