Anti-cancer activity of the cell membrane-permeable phytic acid prodrug

Bioorg Chem. 2019 Nov:92:103240. doi: 10.1016/j.bioorg.2019.103240. Epub 2019 Sep 4.

Abstract

Phytic acid (IP6) is an ingredient in cereals and legumes, and limited amounts of this compound are considered to enter the cell and exert anti-cancer effects. These effects have been seen by studying cells treated with around 1-5 mM IP6. However, such a large amount of IP6 chelates metals and changes the pH in cell culture medium. To overcome this problem, we synthesized a prodrug of IP6 (Pro-IP6) and elucidated generation of IP6 from Pro-IP6 in cells. Cellular experiments using Pro-IP6 demonstrated selective anti-cancer effects including apoptosis and inhibition of Akt activation. Furthermore, an in vivo study using mice with adult T-cell leukemia also showed that Pro-IP6 reduced the size of the cancer. Taken together, Pro-IP6 is a useful biological tool and may lead to development of new anti-cancer drugs.

Keywords: Adult T-cell leukemia; Akt; Anti-cancer activity; Apoptosis; IP6; Phytic acid; Prodrug.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / metabolism
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects*
  • Cell Membrane Permeability / drug effects*
  • Cell Survival / drug effects
  • Dose-Response Relationship, Drug
  • HeLa Cells
  • Humans
  • Jurkat Cells
  • K562 Cells
  • Leukemia, T-Cell / drug therapy
  • Mice
  • Molecular Structure
  • Phytic Acid / chemistry
  • Phytic Acid / metabolism
  • Phytic Acid / pharmacology*
  • Prodrugs / chemistry
  • Prodrugs / metabolism
  • Prodrugs / pharmacology*
  • Xenograft Model Antitumor Assays

Substances

  • Antineoplastic Agents
  • Prodrugs
  • Phytic Acid