@article {48,
	title = {A genistein derivative, ITB-301, induces microtubule depolymerization and mitotic arrest in multidrug-resistant ovarian cancer.},
	journal = {Cancer chemotherapy and pharmacology},
	volume = {68},
	year = {2011},
	month = {10/2011},
	pages = {1033-44},
	abstract = {PURPOSE: To investigate the mechanistic basis of the anti-tumor effect of the compound ITB-301.

METHODS: Chemical modifications of genistein have been introduced to improve its solubility and efficacy. The anti-tumor effects were tested in ovarian cancer cells using proliferation assays, cell cycle analysis, immunofluorescence, and microscopy.

RESULTS: In this work, we show that a unique glycoside of genistein, ITB-301, inhibits the proliferation of SKOv3 ovarian cancer cells. We found that the 50\% growth inhibitory concentration of ITB-301 in SKOv3 cells was 0.5~μM. Similar results were obtained in breast cancer, ovarian cancer, and acute myelogenous leukemia cell lines. ITB-301 induced significant time- and dose-dependent microtubule depolymerization. This depolymerization resulted in mitotic arrest and inhibited proliferation in all ovarian cancer cell lines examined including SKOv3, ES2, HeyA8, and HeyA8-MDR cells. The cytotoxic effect of ITB-301 was dependent on its induction of mitotic arrest as siRNA-mediated depletion of BUBR1 significantly reduced the cytotoxic effects of ITB-301, even at a concentration of 10~μM. Importantly, efflux-mediated drug resistance did not alter the cytotoxic effect of ITB-301 in two independent cancer cell models of drug resistance.

CONCLUSION: These results identify ITB-301 as a novel anti-tubulin agent that could be used in cancers that are multidrug resistant. We propose a structural model for the binding of ITB-301 to α- and β-tubulin dimers on the basis of molecular docking simulations. This model provides a rationale for future work aimed at designing of more potent analogs.},
	keywords = {Antineoplastic Agents, Cell Line, Tumor, Cell Proliferation, Dose-Response Relationship, Drug, Drug Resistance, Multiple, Drug Resistance, Neoplasm, Female, Genistein, Glycosides, Humans, Inhibitory Concentration 50, Microtubules, Mitosis, Models, Molecular, Molecular Dynamics Simulation, Ovarian Neoplasms, Protein Binding, Tubulin},
	issn = {1432-0843},
	doi = {10.1007/s00280-011-1575-2},
	author = {Ahmed, Ahmed Ashour and Goldsmith, Juliet and Fokt, Izabela and Le, Xiao-Feng and Krzy{\'s}ko, Krystiana A and Lesyng, Bogdan and Bast, Robert C and Priebe, Waldemar}
}
@article {52,
	title = {Two novel presenilin 1 gene mutations connected with frontotemporal dementia-like clinical phenotype: genetic and bioinformatic assessment.},
	journal = {Experimental neurology},
	volume = {200},
	year = {2006},
	month = {2006 Jul},
	pages = {82-8},
	abstract = {Mutations in the amyloid precursor protein (APP), presenilin 1 (PSEN1) and presenilin 2 (PSEN2) genes are associated with early-onset familial Alzheimer{\textquoteright}s disease (EOAD). There are several reports describing mutations in PSEN1 in cases with frontotemporal dementia (FTD). We identified two novel mutations in the PSEN1 gene: L226F and L424H. The first mutation was detected in a patient with a clinical diagnosis of FTD and a post-mortem diagnosis of AD. The second mutation is connected with a clinical phenotype of variant AD with strong FTD signs. In silico modeling revealed that the mutations, as well as mutations used for comparison (F177L and L424R), change the local structure, stability and/or properties of the transmembrane regions of the presenilin 1 protein (PS1). In contrast, a silent non-synonymous substitution F175S is eclipsed by external residues and has no influence on PS1 interfacial surface. We suggest that in silico analysis of PS1 substitutions can be used to characterize novel PSEN1 mutations, to discriminate between silent polymorphisms and a potential disease-causing mutation. We also propose that PSEN1 mutations should be considered in FTD patients with no MAPT mutations.},
	keywords = {Adult, Computational Biology, Dementia, Diagnosis, Differential, Female, Genetic Testing, Humans, Male, Membrane Proteins, Models, Molecular, Mutation, Phenotype, Presenilin-1},
	issn = {0014-4886},
	doi = {10.1016/j.expneurol.2006.01.022},
	author = {Zekanowski, Cezary and Golan, Maciej P and Krzy{\'s}ko, Krystiana A and Lipczy{\'n}ska-{\L}ojkowska, Wanda and Filipek, S{\l}awomir and Kowalska, Anna and Rossa, Grzegorz and Pep{\l}o{\'n}ska, Beata and Styczy{\'n}ska, Maria and Maruszak, Aleksandra and Religa, Dorota and Wender, Mieczys{\l}aw and Kulczycki, Jerzy and Barcikowska, Maria and Ku{\'z}nicki, Jacek}
}
