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

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

Author information

1
Dept. of Biochemistry & Medical Genetics, University of Manitoba, Room 333 BMSB, 745 Bannatyne Avenue, Winnipeg, R3E 0 W9, MB, Canada.
2
Dept. of Chemistry, University of Manitoba, Winnipeg, Canada.
3
Dept. of Biochemistry & Medical Genetics, University of Manitoba, Room 333 BMSB, 745 Bannatyne Avenue, Winnipeg, R3E 0 W9, MB, Canada. mark.nachtigal@umanitoba.ca.
4
Dept. of Obstetrics, Gynecology & Reproductive Sciences, University of Manitoba, Winnipeg, Canada. mark.nachtigal@umanitoba.ca.
5
Research Institute in Oncology & Hematology, CancerCare Manitoba, Winnipeg, Canada. mark.nachtigal@umanitoba.ca.
6
Manitoba Ovarian Cancer Outcome (MOCO) study group, Winnipeg, Canada. mark.nachtigal@umanitoba.ca.

Abstract

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

PMID:
28499442
PMCID:
PMC5429581
DOI:
10.1186/s13046-017-0538-9
[Indexed for MEDLINE]
Free PMC Article

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