Novel glycolipid agents for killing cisplatin-resistant human epithelial ovarian cancer cells

J Exp Clin Cancer Res. 2017 May 12;36(1):67. doi: 10.1186/s13046-017-0538-9.


Background: Chemotherapy resistance is one of the major factors contributing to mortality from human epithelial ovarian cancer (EOC). Identifying drugs that can effectively kill chemotherapy-resistant EOC cells would be a major advance in reducing mortality. Glycosylated antitumour ether lipids (GAELs) are synthetic glycolipids that are cytotoxic to a wide range of cancer cells. They appear to induce cancer cell death in an apoptosis-independent manner.

Methods: Herein, the effectiveness of two GAELs, GLN and MO-101, in killing chemotherapy-sensitive and -resistant EOC cells lines and primary cell samples was tested using monolayer, non-adherent aggregate, and non-adherent spheroid cultures.

Results: Our results show that EOC cells exhibit a differential sensitivity to the GAELs. Strikingly, both GAELs are capable of inducing EOC cell death in chemotherapy-sensitive and -resistant cells grown as monolayer or non-adherent cultures. Mechanistic studies provide evidence that apoptotic-cell death (caspase activation) contributes to, but is not completely responsible for, GAEL-induced cell killing in the A2780-cp EOC cell line, but not primary EOC cell samples.

Conclusions: Studies using primary EOC cell samples supports previously published work showing a GAEL-induced caspase-independent mechanism of death. GAELs hold promise for development as novel compounds to combat EOC mortality due to chemotherapy resistance.

Keywords: Drug-resistance; Glycosylated anti-tumour ether lipid; Ovarian cancer; Spheroid.

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects
  • Carcinoma, Ovarian Epithelial
  • Cell Death / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Cells, Cultured
  • Cisplatin / pharmacology*
  • Dose-Response Relationship, Drug
  • Drug Resistance, Neoplasm / drug effects*
  • Glycolipids / pharmacology*
  • Humans
  • Neoplasms, Glandular and Epithelial / metabolism
  • Ovarian Neoplasms / metabolism
  • Pepstatins / pharmacology


  • Antineoplastic Agents
  • Glycolipids
  • Pepstatins
  • Cisplatin
  • pepstatin