title: ZJU-6, a novel derivative of Erianin, shows potent anti-tubulin polymerisation and anti-angiogenic activities.
abstract: ZJU-6 was designed to enhance anti-angiogenesis and anti-tumour activity of its parent compound Erianin, a clinic anti-tumour agent. This study investigated the detailed biological mechanism of ZJU-6 in comparison with that of Erianin. Both ZJU-6 and Erianin substantially reduced cell viability and induced apoptosis in human cancer cell lines. Profound G2/M cell arrest was observed 24 h after treatment of MCF-7 cells with ZJU-6 (≥ 2.5 μM) or Erianin (≥ 0.1 μM); being consistent with mitotic collapse. 0.5 μM of Erianin or ZJU-6 failed to stabilise tubulin. Pre-G1 MCF-7 cell accumulating 24 h post treatment indicated apoptosis. Caspase-3 activity, PARP cleavage and Annexin V + ve /PI -ve populations correlate the apoptotic destiny of cells exposed to either ZJU-6 or Erianin. Furthermore ZJU-6 showed potent anti-angiogenetic property and demonstrated radical scavenging capacity. Due to its potent anti-proliferative, pro-apoptotic and anti-angiogenic activities ZJU-6 is an attractive chemotherapeutic agent to be developed.
authors: School of Pharmacy and Centre for Biomolecular Sciences, University of Nottingham, University Park, Nottingham, NG7 2RD, UK.
authors: Frankie
authors: F
authors: Lam
authors: Tracey D
authors: TD
authors: Bradshaw
authors: Hui
authors: H
authors: Mao
authors: Scott
authors: S
authors: Roberts
authors: Yuanjiang
authors: Y
authors: Pan
authors: Shudong
authors: S
authors: Wang
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D017304:Annexin A5 / Q000378:metabolism; D000970:Antineoplastic Agents / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D001632:Bibenzyls / Q000737:chemistry* / Q000494:pharmacology*; D053148:Caspase 3 / Q000378:metabolism; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D016166:Free Radical Scavengers / Q000494:pharmacology; D016195:G2 Phase / Q000187:drug effects; D006801:Humans; D061986:MCF-7 Cells; D008870:Microtubules / Q000187:drug effects / Q000378:metabolism; D019800:Phenol; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D014404:Tubulin / Q000378:metabolism*
chemical_list: D020533:Angiogenesis Inhibitors; D017304:Annexin A5; D000970:Antineoplastic Agents; D000975:Antioxidants; D001632:Bibenzyls; C477638:Erianin; D016166:Free Radical Scavengers; D014404:Tubulin; D019800:Phenol; D011065:Poly(ADP-ribose) Polymerases; D053148:Caspase 3