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docetaxel-induced polyploidy

Danielle C Chinn, William S Holland, Philip C Mack
PURPOSE: Aurora kinases are key regulators of mitotic events. Dysfunction of these kinases can cause polyploidy and chromosomal instability, a contributor to tumorigenesis. MK-5108 is a potent inhibitor of Aurora A kinase that has shown preclinical potent activity in malignancies of breast, cervical, colon, ovarian, and pancreatic origin. We sought to assess the preclinical efficacy of MK-5108 in a panel of non-small-cell lung cancer cell lines as a single agent and in combination with cisplatin and docetaxel...
July 2014: Journal of Cancer Research and Clinical Oncology
Tammy L Bush, Marc Payton, Scott Heller, Grace Chung, Kelly Hanestad, James B Rottman, Robert Loberg, Gregory Friberg, Richard L Kendall, Douglas Saffran, Robert Radinsky
Breast cancer is the most prevalent malignancy affecting women and ranks second in cancer-related deaths, in which death occurs primarily from metastatic disease. Triple-negative breast cancer (TNBC) is a more aggressive and metastatic subtype of breast cancer that is initially responsive to treatment of microtubule-targeting agents (MTA) such as taxanes. Recently, we reported the characterization of AMG 900, an orally bioavailable, potent, and highly selective pan-Aurora kinase inhibitor that is active in multidrug-resistant cell lines...
November 2013: Molecular Cancer Therapeutics
Juan Hao, Bi-bo Yuan, Yuan-fu Xu, Juan Yu, Guo-yan Liu, De-hua Wang
OBJECTIVE: To investigate the changes of drug sensitivity of spindle poison-induced polyploid tumor cells to chemotherapeutic agents and its possible mechanism. METHODS: Nocodazole in a dose of 100 ng/ml was used to induce polyploidization in a breast cancer cell line MDA-MB-231 cells. The polyploid cells (T-MDA-MB-231) were sorted by flow cytometry. The morphological changes and proliferation of T-MDA-MB-231 cells were compared with that of MDA-MB-231 cells. The cell growth inhibition was assessed by MTT assay...
June 2012: Zhonghua Zhong Liu za Zhi [Chinese Journal of Oncology]
Wenqing Qi, Laurence S Cooke, Xiaobing Liu, Lisa Rimsza, Denise J Roe, Ann Manziolli, Daniel O Persky, Thomas P Miller, Daruka Mahadevan
Auroras (A and B) are oncogenic serine/threonine kinases that play key roles in the mitotic phase of the eukaryotic cell cycle. Analysis of the leukemia lymphoma molecular profiling project (LLMPP) database indicates Aurora over-expression correlates with poor prognosis. A tissue microarray (TMA) composed of 20 paired mantle cell lymphoma (MCL) patients demonstrated >75% of patients had high levels Aurora expression. Aurora A and B were also found elevated in 13 aggressive B-NHL cell lines. MLN8237, an Aurora inhibitor induced G2/M arrest with polyploidy and abrogated Aurora A and histone-H3 phosphorylation...
April 1, 2011: Biochemical Pharmacology
Carolyn Wiltshire, Babloo L Singh, Jacqueline Stockley, Janis Fleming, Brendan Doyle, Robert Barnetson, Craig N Robson, Frank Kozielski, Hing Y Leung
Castrate-resistant prostate cancer remains a major clinical challenge. Due to the toxicity profile of taxane-based chemotherapy and treatment failure in some patients, novel agents with improved efficacy to side effect profiles are urgently needed. Eg5, a member of the kinesin-5 family, controls the formation of the bipolar spindle during cell division, and suppressed Eg5 function leads to mitotic arrest. S-Trityl-L-cysteine (STLC) is a novel Eg5-specific small-molecule inhibitor. Here, we report the first study to evaluate its use in prostate cancer...
June 2010: Molecular Cancer Therapeutics
H L Lin, T Y Liu, G Y Chau, W Y Lui, C W Chi
BACKGROUND: Previously, the authors observed that paclitaxel treatment of hepatoma cells resulted in differential cytotoxicity. Whether other antimicrotubule agents (docetaxel and 2-methoxyestradiol) are more effective than paclitaxel is not clear. Moreover, whether the modulation of reactive oxygen species (ROS) is involved in the drug-induced growth inhibition of hepatoma cells is not known. METHODS: The authors examined the effects of 2-methoxyestradiol, paclitaxel, and docetaxel on HepG2, Hep3B, HA22T/VGH, and Hepa1-6 hepatoma cell lines...
September 1, 2000: Cancer
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