Exploring the multifaceted impact of lanthanides on physiological pathways in human breast cancer cells

Toxicology. 2024 Feb:502:153731. doi: 10.1016/j.tox.2024.153731. Epub 2024 Jan 20.

Abstract

Lanthanum (La) and cerium (Ce), rare earth elements with physical properties similar to calcium (Ca), are generally considered non-toxic when used appropriately. However, their ions possess anti-tumor capabilities. This investigation explores the potential applications and mechanisms of LaCl3 or CeCl3 treatment in triple-negative breast cancer (TNBC) cell lines. TNBC, characterized by the absence of estrogen receptor (ERα), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER-2) expression, is prone to early metastasis and resistant to hormone therapy. Our results demonstrate that La/Ce treatment reduces cell growth, and when combined with cisplatin, it synergistically inhibits cell growth and the PI3K/AKT pathway. La and Ce induce oxidative stress by disrupting mitochondrial function, leading to protein oxidation. Additionally, they interfere with protein homeostasis and induce nucleolar stress. Furthermore, disturbance in F-actin web formation impairs cell migration. This study delves into the mechanism by which calcium-like elements La and Ce inhibit breast cancer cell growth, shedding light on their interference in mitochondrial function, protein homeostasis, and cytoskeleton assembly.

Keywords: Cytoskeleton assembly; Lanthanides; Nucleolar stress; Protein homeostasis; Triple-negative breast cancer.

MeSH terms

  • Calcium
  • Cell Line, Tumor
  • Cisplatin
  • Humans
  • Lanthanoid Series Elements*
  • Lanthanum / toxicity
  • Phosphatidylinositol 3-Kinases / metabolism
  • Triple Negative Breast Neoplasms* / metabolism

Substances

  • Lanthanoid Series Elements
  • Phosphatidylinositol 3-Kinases
  • Calcium
  • Cisplatin
  • Lanthanum