Replacing d-Glucosamine with Its l-Enantiomer in Glycosylated Antitumor Ether Lipids (GAELs) Retains Cytotoxic Effects against Epithelial Cancer Cells and Cancer Stem Cells.
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.
Department of Chemistry, Faculty of Science, University of Manitoba , 144 Dysart Road, Winnipeg, Manitoba R3T 2N2, Canada.
Makanjuola
M
Ogunsina
Department of Biochemistry & Medical Genetics, Faculty of Health Sciences, University of Manitoba , 745 Bannatyne Avenue, Winnipeg, Manitoba R3E 0J9, Canada.
Pranati
P
Samadder
Department of Chemistry, Faculty of Science, University of Manitoba , 144 Dysart Road, Winnipeg, Manitoba R3T 2N2, Canada.
Temilolu
0000-0003-1583-8562
T
Idowu
Department of Biochemistry & Medical Genetics, Faculty of Health Sciences, University of Manitoba , 745 Bannatyne Avenue, Winnipeg, Manitoba R3E 0J9, Canada.
Gilbert
G
Arthur
Department of Chemistry, Faculty of Science, University of Manitoba , 144 Dysart Road, Winnipeg, Manitoba R3T 2N2, Canada.
Frank
0000-0001-8697-5519
F
Schweizer
D004848:Epithelium / Q000378:metabolism*; D005944:Glucosamine / Q000737:chemistry*; D006031:Glycosylation; D006801:Humans; D009369:Neoplasms / Q000378:metabolism*; D014411:Neoplastic Stem Cells / Q000378:metabolism* / Q000473:pathology; D013237:Stereoisomerism
D005944:Glucosamine