Novel glycolipid agents for killing cisplatin-resistant human epithelial ovarian cancer cellsReport as inadecuate




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Journal of Experimental and Clinical Cancer Research

, 36:67

First Online: 12 May 2017Received: 06 February 2017Accepted: 08 May 2017DOI: 10.1186-s13046-017-0538-9

Cite this article as: Moraya, A.I., Ali, J.L., Samadder, P. et al. J Exp Clin Cancer Res 2017 36: 67. doi:10.1186-s13046-017-0538-9

Abstract

BackgroundChemotherapy 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.

MethodsHerein, 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.

ResultsOur 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.

ConclusionsStudies 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.

KeywordsOvarian cancer Drug-resistance Glycosylated anti-tumour ether lipid Spheroid Electronic supplementary materialThe online version of this article doi:10.1186-s13046-017-0538-9 contains supplementary material, which is available to authorized users.





Author: Amani I. Moraya - Jennifer L. Ali - Pranati Samadder - Lisa Liang - Ludivine Coudière Morrison - Tamra E. Werbowetski-O

Source: https://link.springer.com/



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