title: FNC, a novel nucleoside analogue inhibits cell proliferation and tumor growth in a variety of human cancer cells.
abstract: Inhibition of cellular DNA synthesis is a strategy to block cancer cell division. Nucleoside analogues can incorporate into DNA and terminate DNA strand elongation. So far, several nucleoside analogues have been successfully used as anticancer drugs. FNC, 2'-deoxy-2'-β-fluoro-4'-azidocytidine is a novel cytidine analogue which demonstrated potent activity against hepatitis C virus (HCV). To investigate the therapeutic potential of FNC in human cancers we studied its activity in a number of cancer cells in vitro and in vivo. FNC potently inhibited cell proliferation with an IC(50) of 0.95-4.55μM in a variety of aggressive human cancer cell lines including B-cell non-Hodgkin's lymphomas, lung adenocarcinoma and acute myeloid leukemia. Cells treated with FNC exhibited G1 and S cell cycle arrest at high and low dose, respectively, which confirms the mechanism of action of nucleoside analogues. Treatment of B-NHL cell lines with FNC induced apoptosis in a dose and time dependent manner. Finally, mouse xenograft models of hepatocarcinoma (H22), sarcoma (S180) and gastric carcinoma (SGC7901) demonstrated that FNC had significant tumor growth inhibition activity in a dose-dependent manner with low toxicity. Together, our results suggest that FNC may be a valuable therapy in cancer patients and warrant early phase clinical trial evaluation.
authors.affiliation: Department of Chemistry, Zhengzhou University, Zhengzhou, Henan Province, PR China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Wang
authors.forename: Xiaobing
authors.initials: X
authors.lastname: Liu
authors.forename: Qingduan
authors.initials: Q
authors.lastname: Wang
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.forename: Jinhua
authors.initials: J
authors.lastname: Jiang
authors.forename: Xiaohe
authors.initials: X
authors.lastname: Guo
authors.forename: Qingxia
authors.initials: Q
authors.lastname: Fan
authors.forename: Liyun
authors.initials: L
authors.lastname: Zheng
authors.forename: Xuejun
authors.initials: X
authors.lastname: Yu
authors.forename: Ning
authors.initials: N
authors.lastname: Wang
authors.forename: Zhenliang
authors.initials: Z
authors.lastname: Pan
authors.forename: Chuanjun
authors.initials: C
authors.lastname: Song
authors.forename: Wenqing
authors.initials: W
authors.lastname: Qi
authors.forename: Junbiao
authors.initials: J
authors.lastname: Chang
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001386:Azides / Q000494:pharmacology*; D002453:Cell Cycle; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D006801:Humans; D020128:Inhibitory Concentration 50; D051379:Mice
chemical_list: D000970:Antineoplastic Agents; D001386:Azides; D003841:Deoxycytidine; C540945:azvudine