Design, synthesis, and biological activity of a family of novel ceramide analogues in chemoresistant breast cancer cells.
Resistance to chemotherapy and endocrine therapy is a major cause of breast cancer treatment failure. We have synthesized six novel analogues using C8-ceramide as the lead analogue and studied their effect on hormone therapy resistant (MDA-MB-231) and chemoresistant (MCF-7TN-R) breast cancer cells. Pharmacologic intervention using these ceramide analogues inhibited clonogenic survival and induced apoptosis, with one analogue being more effective than C8-ceramide. Our results show ceramide-based therapy has therapeutic potential in treating drug resistant breast cancer.
Antoon
James W
JW
Department of Pharmacology and Department of Medicine, Tulane University School of Medicine, 1430 Tulane Avenue, New Orleans, Louisiana 70112, USA.
Liu
Jiawang
J
Gestaut
Matthew M
MM
Burow
Matthew E
ME
Beckman
Barbara S
BS
Foroozesh
Maryam
M
D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002518:Ceramides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D015195:Drug Design; D019008:Drug Resistance, Neoplasm; D006728:Hormones / Q000494:pharmacology; D006801:Humans; D020128:Inhibitory Concentration 50; D008246:Lysophospholipids / Q000378:metabolism; D013110:Sphingosine / Q000031:analogs & derivatives / Q000378:metabolism
D000970:Antineoplastic Agents; D002518:Ceramides; D006728:Hormones; D008246:Lysophospholipids; C060506:sphingosine 1-phosphate; D013110:Sphingosine