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

Autor: Amani I. Moraya, Jennifer L. Ali, Pranati Samadder, Lisa Liang, Ludivine Coudière Morrison, Tamra E. Werbowetski-Ogilvie, Makanjuola Ogunsina, Frank Schweizer, Gilbert Arthur, Mark W. Nachtigal
Jazyk: angličtina
Rok vydání: 2017
Předmět:
Zdroj: Journal of Experimental & Clinical Cancer Research, Vol 36, Iss 1, Pp 1-13 (2017)
Druh dokumentu: article
ISSN: 1756-9966
DOI: 10.1186/s13046-017-0538-9
Popis: 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.
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