The role of folic acid in inducing of apoptosis by zinc(II) complex in ovary and cervix cancer cells

Mol Divers. 2022 Jun;26(3):1545-1555. doi: 10.1007/s11030-021-10293-5. Epub 2021 Aug 20.

Abstract

Herein, the synthesis, structure, binding affinity, cytotoxicity, and apoptotic properties of the new Zn(II) complex composed of folic acid and bipyridine ligands are reported. Because folic acid has the ability to target cancer cells directly, so it can play a role in targeted drug delivery of the complex and be useful to distinguish normal cells from cancerous. After characterization of Zinc complex utilizing FTIR, EA, and NMR, the results of MTT assay were shown that viability levels of two FR-positive cell lines (HeLa and Ovcar-3) are dependent on time and concentration of [Zn(bpy)FA], whereas, did not show a significant effect on FR-negative cell lines (A549). Also, Real-time PCR revealed that the presence of FA can influence the expression of apoptosis in cervical carcinoma HeLa cells while cisplatin alone doesn't have the ability to trigger apoptosis. Furthermore, the experimental results were evaluated using pharmacophore modeling and molecular docking analysis. Finally, the stability of the Zn(II) complex was surveyed using quantum mechanical studies.

Keywords: Drug Delivery; Folate receptor-positive cell lines; Molecular Docking; Real-time PCR; Zn(II) complex.

MeSH terms

  • Apoptosis
  • Cell Line, Tumor
  • Female
  • Folic Acid / chemistry
  • Folic Acid / metabolism
  • Folic Acid / pharmacology
  • HeLa Cells
  • Humans
  • Molecular Docking Simulation
  • Ovarian Neoplasms* / drug therapy
  • Uterine Cervical Neoplasms* / drug therapy
  • Zinc / chemistry

Substances

  • Folic Acid
  • Zinc