title: Carbohydrate-based inducers of cellular stress for targeting cancer cells.
abstract: Small molecules that block the altered metabolism in cancer or increase the production of reactive oxygen species (ROS) are emerging as potential anti-cancer agents. Considering that various carbohydrates can be used for cellular energetics or protein N-glycosylation of which interruption can lead to cellular stress, we have synthesized and evaluated a library of N-aryl glycosides for induction of ROS and cytotoxicity in H1299 cancer cell line. Two N-aryl glycosides (K8 and H8) were identified that induce about 2-fold induction of ROS and cytotoxicity in H1299 cells. We further showed that the acetylated form of K8 (K8A) activates AMPK, and stabilizes p53 in HEK293 cells, and induce a higher cytotoxicity than 2-deoxy-d-glucose in H1299 cell line.
authors.affiliation: Department of Chemistry, Wayne State University, 5101 Cass Ave, Detroit, MI 48202, USA.
authors.forename: Fidelis T
authors.initials: FT
authors.lastname: Ndombera
authors.affiliation: Department of Chemistry, Wayne State University, 5101 Cass Ave, Detroit, MI 48202, USA.
authors.forename: Garrett C
authors.initials: GC
authors.lastname: VanHecke
authors.affiliation: Department of Chemistry, Wayne State University, 5101 Cass Ave, Detroit, MI 48202, USA.
authors.forename: Shima
authors.initials: S
authors.lastname: Nagi
authors.affiliation: Department of Chemistry, Wayne State University, 5101 Cass Ave, Detroit, MI 48202, USA.
authors.forename: Young-Hoon
authors.initials: YH
authors.lastname: Ahn
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006027:Glycosides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D057809:HEK293 Cells; D006801:Humans; D015394:Molecular Structure; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013312:Stress, Physiological / Q000187:drug effects*; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D006027:Glycosides; D017382:Reactive Oxygen Species
keywords: 2-Deoxy-d-glucose; Cytotoxicity; N-Aryl glycoside library; Reactive oxygen species inducer