Role of the transient receptor potential melastatin 4 in inhibition effect of arsenic trioxide on the tumor biological features of colorectal cancer cell

PeerJ. 2024 Jun 4:12:e17559. doi: 10.7717/peerj.17559. eCollection 2024.

Abstract

Background: To investigate the effects of arsenic trioxide (ATO) on human colorectal cancer cells (HCT116) growth and the role of transient receptor potential melastatin 4 (TRPM4) channel in this process.

Methods: The viability of HCT116 cells was assessed using the CCK-8 assay. Western blot analysis was employed to examine the protein expression of TRPM4. The apoptosis of HCT116 cells was determined using TUNEL and Flow cytometry. Cell migration was assessed through the cell scratch recovery assay and Transwell cell migration assay. Additionally, Transwell cell invasion assay was performed to determine the invasion ability of HCT116 cells.

Results: ATO suppressed the viability of HCT116 cells in a dose-dependent manner, accompanied by a decline in cell migration and invasion, and an increase in apoptosis. 9-phenanthroline (9-Ph), a specific inhibitor of TRPM4, abrogated the ATO-induced upregulation of TRPM4 expression. Additionally, blocking TRPM4 reversed the effects of ATO on HCT116 cells proliferation, including restoration of cell viability, migration and invasion, as well as the inhibition of apoptosis.

Conclusion: ATO inhibits CRC cell growth by inducing TRPM4 expression, our findings indicate that ATO is a promising therapeutic strategy and TRPM4 may be a novel target for the treatment of CRC.

Keywords: Arsenic trioxide; Colorectal cancer; HCT116 cells; TRPM4 channel.

MeSH terms

  • Antineoplastic Agents / pharmacology
  • Apoptosis* / drug effects
  • Arsenic Trioxide* / pharmacology
  • Arsenicals / pharmacology
  • Cell Movement* / drug effects
  • Cell Proliferation* / drug effects
  • Cell Survival* / drug effects
  • Colorectal Neoplasms* / drug therapy
  • Colorectal Neoplasms* / metabolism
  • Colorectal Neoplasms* / pathology
  • HCT116 Cells
  • Humans
  • Neoplasm Invasiveness
  • Oxides / pharmacology
  • TRPM Cation Channels* / antagonists & inhibitors
  • TRPM Cation Channels* / genetics
  • TRPM Cation Channels* / metabolism

Substances

  • TRPM Cation Channels
  • Arsenic Trioxide
  • TRPM4 protein, human
  • Oxides
  • Antineoplastic Agents
  • Arsenicals

Grants and funding

This work was supported by the Heilongjiang Postdoctoral Special Fund (LBH–Q19155) and the Outstanding Youth Fund of School of Pharmacy of Harbin Medical University (2019-YQ-01). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.