Anticancer activity of a ceramide analog containing a disulfide linkage.
The effects of exogenous short-chain ceramide (1) on the arrest of growth of cancer cells in vitro and induction of apoptosis have been well documented. In the present study, an analog of 1 with a disulfide linkage, N-(4',5'-dithiaheptanoyl)-D-erythro-ceramide (2), was synthesized and found to be significantly more antiproliferative and cytotoxic than 1 in BT549, A549, and DU145 cancer cells. The activity was correlated with a reduction in cellular glutathione (GSH) level. Ceramide analogs with a tri- and tetra-sulfide moiety were also prepared, but they did not deplete cellular GSH levels and did not possess antiproliferative or cytotoxic properties.
Bittman
Robert
R
Department of Chemistry and Biochemistry, Queens College of the City University of New York, Flushing, NY 11367, USA.
Li
Zaiguo
Z
Samadder
Pranati
P
Arthur
Gilbert
G
D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D002518:Ceramides / Q000737:chemistry / Q000494:pharmacology*; D004220:Disulfides / Q000737:chemistry*; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D008956:Models, Chemical; D015394:Molecular Structure; D013997:Time Factors
D000970:Antineoplastic Agents; D002518:Ceramides; D004220:Disulfides; C520703:N-(4',5'-dithiaheptanoyl)-D-erythro-ceramide; D020169:Caspases; D005978:Glutathione