Amphiphilic Modulation of Glycosylated Antitumor Ether Lipids Results in a Potent Triamino Scaffold against Epithelial Cancer Cell Lines and BT474 Cancer Stem Cells.

Item request has been placed! ×
Item request cannot be made. ×
loading   Processing Request
Read More Add to Saved list
  • Additional Information
    • Source:
      Publisher: American Chemical Society Country of Publication: United States NLM ID: 9716531 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1520-4804 (Electronic) Linking ISSN: 00222623 NLM ISO Abbreviation: J Med Chem Subsets: MEDLINE
    • Publication Information:
      Publication: Washington Dc : American Chemical Society
      Original Publication: [Easton, Pa.] : American Chemical Society, [c1963-
    • Subject Terms:
      Antineoplastic Agents/*chemistry ; Antineoplastic Agents/*pharmacology ; Epithelial Cells/*drug effects ; Lipids/*chemistry ; Lipids/*pharmacology ; Neoplastic Stem Cells/*drug effects; Amination ; Cell Line, Tumor ; Cell Survival/drug effects ; Epithelial Cells/pathology ; Glycosylation ; Humans ; Neoplasms/drug therapy ; Neoplasms/pathology ; Neoplastic Stem Cells/pathology
    • Abstract:
      The problems of resistance to apoptosis-inducing drugs, recurrence, and metastases that have bedeviled cancer treatment have been attributed to the presence of cancer stem cells (CSCs) in tumors, and there is currently no clinically indicated drug for their eradication. We previously reported that glycosylated antitumor ether lipids (GAELs) display potent activity against CSCs. Here, we show that by carefully modulating the amphiphilic nature of a monoamine-based GAEL, we can generate a potent triamino scaffold that is active against a panel of hard-to-kill epithelial cancer cell lines (including triple-negative breast) and BT474 CSCs. The most active compound of this set, which acts via a nonmembranolytic, nonapoptotic caspase-independent mechanism, is more effective than cisplatin and doxorubicin against these cell lines and more potent than salinomycin against BT474 CSCs. Understanding the combination of factors crucial for the enhanced cytotoxicity of GAELs opens new avenues to develop potent compounds against drug-resistant cancer cells and CSCs.
    • Accession Number:
      0 (Antineoplastic Agents)
      0 (Lipids)
    • Publication Date:
      Date Created: 20171019 Date Completed: 20171229 Latest Revision: 20190115
    • Publication Date:
      20231215
    • Accession Number:
      10.1021/acs.jmedchem.7b01198
    • Accession Number:
      29043812