Antiproliferative, Cytotoxic, and Apoptotic Activity of Steroidal Oximes in Cervicouterine Cell Lines

Molecules. 2016 Nov 14;21(11):1533. doi: 10.3390/molecules21111533.

Abstract

Steroidal sapogenins have shown antiproliferative effects against several tumor cell lines; and their effects on human cancer cells are currently under study. Changes in the functionality on the steroidal structure make it possible to modify the biological activity of compounds. Herein, we report the synthesis and in vitro antitumor activity of two steroidal oxime compounds on cervical cancer cells. These derivatives were synthesized from the steroidal sapogenin diosgenin in good yields. The in vitro assays show that the steroidal oximes show significant antiproliferative activity compared to the one observed for diosgenin. Cell proliferation, cell death, and the cytotoxic effects were determined in both cervical cancer cells and human lymphocytes. The cancer cells showed apoptotic morphology and an increased presence of active caspase-3, providing the notion of a death pathway in the cell. Significantly, the steroidal oximes did not exert a cytotoxic effect on lymphocytes.

Keywords: (25R)-spirost-4-en-3,6-dione; 23-acetyldiosgenin; antiproliferative activity; apoptosis; steroidal oximes.

MeSH terms

  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology
  • Apoptosis
  • Caspase 3 / metabolism
  • Cell Cycle / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Diosgenin / analogs & derivatives
  • Drug Screening Assays, Antitumor
  • Female
  • Gene Expression Regulation, Neoplastic / drug effects
  • HeLa Cells
  • Humans
  • Oximes / chemical synthesis*
  • Oximes / chemistry
  • Oximes / pharmacology*
  • Signal Transduction / drug effects
  • Steroids / chemical synthesis*
  • Steroids / chemistry
  • Steroids / pharmacology*

Substances

  • Antineoplastic Agents
  • Oximes
  • Steroids
  • CASP3 protein, human
  • Caspase 3
  • Diosgenin