In vivo and in vitro properties of STX2484: a novel non-steroidal anti-cancer compound active in taxane-resistant breast cancer

C Stengel, S P Newman, J M Day, S K Chander, F L Jourdan, M P Leese, E Ferrandis, S Regis-lydi, B V L Potter, M J Reed, A Purohit, P A Foster

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Background:
STX2484 is a novel non-steroidal compound with potent anti-proliferative activity. These studies aimed to identify STX2484’s mechanism of action, in vivo efficacy and activity in taxane-resistant breast cancer models.
Methods:
Effects of STX2484 and paclitaxel on proliferation, cell cycle and apoptosis were assessed in vitro in drug-resistant (MCF-7DOX) and non-resistant cells (MCF-7WT). STX2484 efficacy in βIII tubulin overexpression in MCF-7 cells was also determined. Anti-angiogenic activity was quantified in vitro by a co-culture model and in vivo using a Matrigel plug assay. An MDA-MB-231 xenograft model was used to determine STX2484 efficacy in vivo.
Results:
STX2484 is a tubulin disruptor, which induces p53 expression, Bcl2 phosphorylation, caspase-3 cleavage, cell cycle arrest and apoptosis. In addition, STX2484 is a potent anti-angiogenic agent in vitro and in vivo. In breast cancer xenografts, STX2484 (20 mg kg−1 p.o.) suppressed tumour growth by 84% after 35 days of daily dosing, with limited toxicity. In contrast to paclitaxel, STX2484 efficacy was unchanged in two clinically relevant drug-resistant models.
Conclusions:
STX2484 is an orally bioavailable microtubule-disrupting agent with in vivo anti-angiogenic activity and excellent in vivo efficacy with no apparent toxicity. Crucially, STX2484 has superior efficacy to paclitaxel in models of clinical drug resistance.
Original languageEnglish
Pages (from-to)300-308
JournalBritish Journal of Cancer
Volume111
Issue number2
DOIs
Publication statusPublished - 15 Jul 2015

Fingerprint Dive into the research topics of 'In vivo and in vitro properties of STX2484: a novel non-steroidal anti-cancer compound active in taxane-resistant breast cancer'. Together they form a unique fingerprint.

  • Cite this

    Stengel, C., Newman, S. P., Day, J. M., Chander, S. K., Jourdan, F. L., Leese, M. P., Ferrandis, E., Regis-lydi, S., Potter, B. V. L., Reed, M. J., Purohit, A., & Foster, P. A. (2015). In vivo and in vitro properties of STX2484: a novel non-steroidal anti-cancer compound active in taxane-resistant breast cancer. British Journal of Cancer, 111(2), 300-308. https://doi.org/10.1038/bjc.2014.188