Replacing d-Glucosamine with Its l-Enantiomer in Glycosylated Antitumor Ether Lipids (GAELs) Retains Cytotoxic Effects against Epithelial Cancer Cells and Cancer Stem Cells

Makanjuola Ogunsina; Pranati Samadder; Temilolu Idowu; Gilbert Arthur; Frank Schweizer

doi:10.1021/acs.jmedchem.6b01773

Replacing d-Glucosamine with Its l-Enantiomer in Glycosylated Antitumor Ether Lipids (GAELs) Retains Cytotoxic Effects against Epithelial Cancer Cells and Cancer Stem Cells

J Med Chem. 2017 Mar 9;60(5):2142-2147. doi: 10.1021/acs.jmedchem.6b01773. Epub 2017 Feb 21.

Authors

Makanjuola Ogunsina¹, Pranati Samadder², Temilolu Idowu¹, Gilbert Arthur², Frank Schweizer¹

Affiliations

¹ Department of Chemistry, Faculty of Science, University of Manitoba , 144 Dysart Road, Winnipeg, Manitoba R3T 2N2, Canada.
² Department of Biochemistry & Medical Genetics, Faculty of Health Sciences, University of Manitoba , 745 Bannatyne Avenue, Winnipeg, Manitoba R3E 0J9, Canada.

PMID: 28177244
DOI: 10.1021/acs.jmedchem.6b01773

Abstract

We describe metabolically inert l-glucosamine-based glycosylated antitumor ether lipids (L-GAELs) that retain the cytotoxic effects of the D-GAELs including the ability to kill BT-474 breast cancer stem cells (CSCs). When compared to adriamycin, cisplatin, and the anti-CSC agent salinomycin, L-GAELs display superior activity to kill cancer stem cells (CSCs). Mode of action studies indicate that L-GAELs like the D-GAELs kill cells via an apoptosis-independent mechanism that was not due to membranolytic effects.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Epithelium / metabolism*
Glucosamine / chemistry*
Glycosylation
Humans
Neoplasms / metabolism*
Neoplastic Stem Cells / metabolism*
Neoplastic Stem Cells / pathology
Stereoisomerism

Substances

Glucosamine