title: Novel indolyl-chalcones target stathmin to induce cancer cell death.
abstract: Efficacy of current therapies for advanced and metastatic cancers remains a challenge in clinical practice. We investigated the anti-cancer potency of 3 novel indoly-chalcones (CITs). Our results indicated the lead molecule CIT-026 (Formula = C20H16FNO) induced cell death in prostate and lung cancer cell lines at sub-micromolar concentration. CITs (CIT-026, CIT-214, CIT-223) lead to microtubule destabilization, cell death and low cell proliferation, which in part was dependent on stathmin (STMN1) expression. Knockdown of STMN1 with siRNA against STMN1 in part restored viability of cancer cells in response to CITs. Further, CIT-026 and CIT-223 blocked cancer cell invasion through matrigel-coated chambers. Mechanistically, CITs inhibited phosphorylation of STMN1 leading to STMN1 accumulation and mitotic catastrophe. In summary, we have synthetized novel anti-cancer CIT molecules and defined their mechanism of action in vitro.
authors.affiliation: a Department of Surgery , Beth Israel Deaconess Medical Center, Harvard Medical School , Boston , MA , USA.|b Transplant Institute & Cancer Research Institute, Beth Israel Deaconess Medical Center , Harvard Medical School , Boston , MA , USA.
authors.forename: Barbara
authors.initials: B
authors.lastname: Wegiel
authors.affiliation: a Department of Surgery , Beth Israel Deaconess Medical Center, Harvard Medical School , Boston , MA , USA.|c Center for Drug Discovery and Translational Research , Beth Israel Deaconess Medical Center , Harvard Medical School , Boston , MA , USA.
authors.forename: Yiqiang
authors.initials: Y
authors.lastname: Wang
authors.affiliation: a Department of Surgery , Beth Israel Deaconess Medical Center, Harvard Medical School , Boston , MA , USA.|b Transplant Institute & Cancer Research Institute, Beth Israel Deaconess Medical Center , Harvard Medical School , Boston , MA , USA.
authors.forename: Mailin
authors.initials: M
authors.lastname: Li
authors.affiliation: a Department of Surgery , Beth Israel Deaconess Medical Center, Harvard Medical School , Boston , MA , USA.|c Center for Drug Discovery and Translational Research , Beth Israel Deaconess Medical Center , Harvard Medical School , Boston , MA , USA.
authors.forename: Finith
authors.initials: F
authors.lastname: Jernigan
authors.affiliation: a Department of Surgery , Beth Israel Deaconess Medical Center, Harvard Medical School , Boston , MA , USA.|c Center for Drug Discovery and Translational Research , Beth Israel Deaconess Medical Center , Harvard Medical School , Boston , MA , USA.
authors.forename: Lijun
authors.initials: L
authors.lastname: Sun
mesh_terms: D001706:Biopsy; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D047188:Chalcones / Q000494:pharmacology*; D006801:Humans; D007211:Indoles / Q000494:pharmacology*; D008870:Microtubules / Q000187:drug effects / Q000378:metabolism; D058990:Molecular Targeted Therapy; D009361:Neoplasm Invasiveness; D009369:Neoplasms / Q000473:pathology*; D010766:Phosphorylation / Q000187:drug effects; D054852:Small Molecule Libraries / Q000494:pharmacology; D050777:Stathmin / Q000378:metabolism*
chemical_list: D047188:Chalcones; D007211:Indoles; D054852:Small Molecule Libraries; D050777:Stathmin
keywords: cell death; inodyl-chalcones; mitosis; stathmin