title: Chemically synthesized sugar-cholestanols possess a preferential anticancer activity involving promising therapeutic potential against human esophageal cancer.
abstract: The understanding of the cell signaling pathways and the molecular events leading to cell death of cancer cells will provide in-depth perspective into the identification and development of potent anticancer agents. A balance between cell proliferation and cell death has been raised as a rational target for the management of malignant tumors. In the present study, the authors demonstrated that chemically synthesized sugar-cholestanols consisting of GlcNAcbeta-, Galbeta- and GlcNAcbeta1,3Galbeta-cholestanols exerted a strong inhibiting activity against cell proliferation of esophageal cancer cells, but cholestanol itself did not show such an activity against the same cancer cells at all. In addition to their predominant role as an antiproliferation agent, evidence based on the molecular analyses suggested that sugar-cholestanols played a regulatory role in multiple signal transduction pathways inducing apoptosis through both the death signal-extrinsic and the mitochondria-intrinsic pathways. Sugar-cholestanols seemed to be more susceptible to esophageal cancer cells than to non-cancerous esophageal cells at the very early event of their exposure and, further, to suppress specifically the expression of vascular endothelial growth factor. Taken together, these novel functions of sugar-cholestanols indicate that they could have promising therapeutic potential against human esophageal cancer.
authors.affiliation: Department of General Surgical Science (Surgery I), Graduate School of Medicine, Gunma University, 3-39-22 Showa-machi, Maebashi, Gunma 371-8511, Japan. afaried@med.gunma-u.ac.jp
authors.forename: Ahmad
authors.initials: A
authors.lastname: Faried
authors.forename: Leri S
authors.initials: LS
authors.lastname: Faried
authors.forename: Takashi
authors.initials: T
authors.lastname: Nakagawa
authors.forename: Takahito
authors.initials: T
authors.lastname: Yamauchi
authors.forename: Mami
authors.initials: M
authors.lastname: Kitani
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Sasabe
authors.forename: Toyo
authors.initials: T
authors.lastname: Nishimura
authors.forename: Nurhayat
authors.initials: N
authors.lastname: Usman
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kato
authors.forename: Takayuki
authors.initials: T
authors.lastname: Asao
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kuwano
authors.forename: Shin
authors.initials: S
authors.lastname: Yazawa
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D020169:Caspases / Q000378:metabolism; D002460:Cell Line; D002461:Cell Line, Transformed; D045744:Cell Line, Tumor; D002777:Cholestanols / Q000138:chemical synthesis* / Q000494:pharmacology*; D004789:Enzyme Activation; D004938:Esophageal Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D006131:Growth Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology; D006801:Humans; D009844:Oligosaccharides / Q000138:chemical synthesis* / Q000494:pharmacology*; D011065:Poly(ADP-ribose) Polymerases / Q000096:biosynthesis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D015854:Up-Regulation / Q000502:physiology; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis
chemical_list: D000970:Antineoplastic Agents; D002777:Cholestanols; D006131:Growth Inhibitors; D009844:Oligosaccharides; D019253:Proto-Oncogene Proteins c-bcl-2; D042461:Vascular Endothelial Growth Factor A; D011065:Poly(ADP-ribose) Polymerases; D020169:Caspases