The Impact of Iron Chelators on the Biology of Cancer Stem Cells

Int J Mol Sci. 2021 Dec 22;23(1):89. doi: 10.3390/ijms23010089.

Abstract

Neoplastic diseases are still a major medical challenge, requiring a constant search for new therapeutic options. A serious problem of many cancers is resistance to anticancer drugs and disease progression in metastases or local recurrence. These characteristics of cancer cells may be related to the specific properties of cancer stem cells (CSC). CSCs are involved in inhibiting cells' maturation, which is essential for maintaining their self-renewal capacity and pluripotency. They show increased expression of transcription factor proteins, which were defined as stemness-related markers. This group of proteins includes OCT4, SOX2, KLF4, Nanog, and SALL4. It has been noticed that the metabolism of cancer cells is changed, and the demand for iron is significantly increased. Iron chelators have been proven to have antitumor activity and influence the expression of stemness-related markers, thus reducing chemoresistance and the risk of tumor cell progression. This prompts further investigation of these agents as promising anticancer novel drugs. The article presents the characteristics of stemness markers and their influence on the development and course of neoplastic disease. Available iron chelators were also described, and their effects on cancer cells and expression of stemness-related markers were analyzed.

Keywords: cancer stem cells; deferasirox; deferoxamine; iron chelators; stemness markers.

Publication types

  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology
  • Drug Resistance, Neoplasm / drug effects
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Iron Chelating Agents / pharmacology*
  • Neoplastic Stem Cells / drug effects*
  • Neoplastic Stem Cells / metabolism
  • Transcription Factors / metabolism

Substances

  • Antineoplastic Agents
  • Iron Chelating Agents
  • Transcription Factors