Novel indolyl-chalcones target stathmin to induce cancer cell death
Open Access
- 17 March 2016
- journal article
- other
- Published by Taylor & Francis Ltd in Cell Cycle
- Vol. 15 (9), 1288-1294
- https://doi.org/10.1080/15384101.2016.1160980
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.Keywords
This publication has 37 references indexed in Scilit:
- RETRACTED ARTICLE: STMN-1 is a potential marker of lymph node metastasis in distal esophageal adenocarcinomas and silencing its expression can reverse malignant phenotype of tumor cellsBMC Cancer, 2014
- Mitosis-targeted anti-cancer therapies: where they standCell Death & Disease, 2012
- Novel role of stathmin in microtubule‐dependent control of endothelial permeabilityThe FASEB Journal, 2012
- Synthesis and Evaluation of Indole-Based Chalcones as Inducers of Methuosis, a Novel Type of Nonapoptotic Cell DeathJournal of Medicinal Chemistry, 2012
- Drugs that target dynamic microtubules: A new molecular perspectiveMedicinal Research Reviews, 2011
- Stathmin1 overexpression associated with polyploidy, tumor‐cell invasion, early recurrence, and poor prognosis in human hepatomaMolecular Carcinogenesis, 2010
- Cell Surface Biliverdin Reductase Mediates Biliverdin-induced Anti-inflammatory Effects via Phosphatidylinositol 3-Kinase and AktOnline Journal of Public Health Informatics, 2009
- Regulation of Microtubule Dynamic Instability in Vitro by Differentially Phosphorylated StathminOnline Journal of Public Health Informatics, 2009
- Gene expression profiles of prostate cancer reveal involvement of multiple molecular pathways in the metastatic processBMC Cancer, 2007
- Identification of Op18/stathmin as a potential target of ASK1‐p38 MAP kinase cascadeJournal of Cellular Physiology, 2005