Suppression of TRPM7 enhances TRAIL-induced apoptosis in triple-negative breast cancer cells

Chiman Song, Seunghye Choi, Ki Bong Oh, Taebo Sim

Research output: Contribution to journalArticlepeer-review

14 Citations (Scopus)


Transient receptor potential cation channel subfamily M member 7 (TRPM7) composed of an ion channel and a kinase domain regulates triple-negative breast cancer (TNBC) cell migration, invasion, and metastasis, but it does not modulate TNBC proliferation. However, previous studies have shown that the combination treatment of nonselective TRPM7 channel inhibitors (2-aminoethoxydiphenyl borate and Gd3+) with tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) increases antiproliferative effects and apoptosis in prostate cancer cells and hepatic stellate cells. We, therefore, investigated the potential role of TRPM7 in proliferation and apoptosis of TNBC cells (MDA-MB-231 and MDA-MB-468 cells) with TRAIL. We demonstrated that suppression of TRPM7 via TRPM7 knockdown or pharmacological inhibition synergistically increases TRAIL-induced antiproliferative effects and apoptosis in TNBC cells. Furthermore, we showed that the synergistic interaction might be associated with TRPM7 channel activities using combination treatments of TRAIL and TRPM7 inhibitors (NS8593 as a TRPM7 channel inhibitor and TG100-115 as a TRPM7 kinase inhibitor). We reveal that downregulation of cellular FLICE-inhibitory protein via inhibition of Ca2+ influx might be involved in the synergistic interaction. Our study would provide both a new role of TRPM7 in TNBC cell apoptosis and a potential combinatorial therapeutic strategy using TRPM7 inhibitors with TRAIL in the treatment of TNBC.

Original languageEnglish
Pages (from-to)10037-10050
Number of pages14
JournalJournal of Cellular Physiology
Issue number12
Publication statusPublished - 2020 Dec 1


  • TRPM7
  • apoptosis
  • c-FLIP
  • triple-negative breast cancer

ASJC Scopus subject areas

  • Physiology
  • Clinical Biochemistry
  • Cell Biology


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