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The University of Manitoba

Pranati Samadder

Frank Schweizer

Gilbert Arthur

Temilolu Idowu

Makanjuola Ogunsina

Yaozu Xu

Glycosylated antitumor ether lipids (GAELs) are effective cytotoxic agents against cancer stem cells. Furthermore, combining GAELs which kill cells by a caspase-independent pathway with agents that kill cells by apoptosis will lead to elimination of the differentiated tumor cells and the undifferentiated cancer stem cells leading to an elimination of the tumor and preventing recurrence.

Glycosylated antitumor ether lipids as novel cancer stem cell cytotoxic agents

Glycosylated Antitumor Ether Lipids (GAELs) kill cancer cells by a nonapoptotic pathway which is an attractive strategy to avoid resistance. To further optimize the antitumor effect, we prepared various analogs of di-, and tri-cationic GAEL analogs differing in the nature of the sugar (D-glucose or L-glucose), the anomeric linkage as well as position of the glycerolipid moiety. The di- and tri-cationic GAELs were synthesized and their in vitro anticancer properties were evaluated against drug resistant and aggressively growing cancer cell lines derived from human breast, prostate, pancreatic and ovarian cancers. The most potent dicationic GAEL analogs were also studied against cancer stem cells obtained from breast BT 474, prostate DU145 and ovarian A2780cp cell lines. Our results indicate that the number of positive charges, the position of the amino substituents and the nature of the sugar have significant effects on the anticancer activities of these compounds. The most active analog kill 50% of the cells at concentration range of 0.5-5 &#x3bc;M and 90% of the cells at the concentration of 1-10 &#x3bc;M depending on type of cancer cells.

Di- and tri-cationic glycosylated antitumor ether lipids, L-gucosylated gaels and rhamnose-linked gaels as cytotoxic agents against epithelial cancer cells and cancer stem cells

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Winnipeg, Canada

Pranati Samadder