4′-Methoxy-2-styrylchromone a novel microtubule-stabilizing antimitotic agent

• Type: Article in International Scientific Journal
• Date: 2008

Authors

Joana Marinho (Author) Other; Madalena Pedro (Author) Other; Diana C.G.A. Pinto (Author) Other; Artur M.S. Silva (Author) Other; José A.S. Cavaleiro (Author) Other; Claudio E. Sunkel (Author) Other; Maria São José Nascimento (Author) FFUP

Journal

Title: Biochemical Pharmacology

Vol. 75 No. 4

Pages: 826-835

ISSN: 0006-2952

Publisher: Elsevier

Indexing

Scopus

Scientific classification

FOS: Medical and Health sciences > Other medical sciences

CORDIS: Health sciences

Other information

Resumo (PT): 4′-Methoxy-2-styrylchromone, a new synthetic chromone was identified as a selective proliferation inhibitor of human tumor (MCF-7 and NCI-H460) cell lines than to non-tumor cells (MRC-5). The antiproliferative activity of this chromone was also extensive to peripheral human lymphocytes. 4′-Methoxy-2-styrylchromone was found to block tumor cells in the G2/M phase of the cell cycle. The G2/M arrest of NCI-H460 cells was dose- and time-dependent, reaching a maximum after 12-h treatment while MCF-7 cells reached the maximum value of G2/M accumulation only after a 24-h treatment. Chromone-treated cells evidenced a high frequency of cells in prometaphase, indicating progression beyond G2 and arrest early in mitosis. This mitotic arrest was associated with abnormal mitotic spindles characterized by the formation of a monopolar structure, suggesting that the chromone interferes with microtubules. The results of an in vitro tubulin polymerization assay showed that this chromone stabilizes microtubules in a manner similar to paclitaxel. <br> <br> Keywords: 2-Styrylchromone; Antimitotic drugs; Tubulin; Mitosis; Cell cycle; Cancer chemotherapy <br> <a target="_blank" href="http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6T4P-4PYGVR7-3&_user=2460038&_coverDate=02%2F15%2F2008&_rdoc=5&_fmt=high&_orig=browse&_origin=browse&_zone=rslt_list_item&_srch=doc-info(%23toc%234980%232008%23999249995%23679515%23FLA%23display%23Volume)&_cdi=4980&_sort=d&_docanchor=&_ct=22&_acct=C000057398&_version=1&_urlVersion=0&_userid=2460038&md5=8bb5601e8c80c87e13c61b40ceaf158a&searchtype=a">Texto integral</a> <br> <br>

Abstract (EN): 4′-Methoxy-2-styrylchromone, a new synthetic chromone was identified as a selective proliferation inhibitor of human tumor (MCF-7 and NCI-H460) cell lines than to non-tumor cells (MRC-5). The antiproliferative activity of this chromone was also extensive to peripheral human lymphocytes. 4′-Methoxy-2-styrylchromone was found to block tumor cells in the G2/M phase of the cell cycle. The G2/M arrest of NCI-H460 cells was dose- and time-dependent, reaching a maximum after 12-h treatment while MCF-7 cells reached the maximum value of G2/M accumulation only after a 24-h treatment. Chromone-treated cells evidenced a high frequency of cells in prometaphase, indicating progression beyond G2 and arrest early in mitosis. This mitotic arrest was associated with abnormal mitotic spindles characterized by the formation of a monopolar structure, suggesting that the chromone interferes with microtubules. The results of an in vitro tubulin polymerization assay showed that this chromone stabilizes microtubules in a manner similar to paclitaxel. <br> <br> Keywords: 2-Styrylchromone; Antimitotic drugs; Tubulin; Mitosis; Cell cycle; Cancer chemotherapy <br> <a target="_blank" href="http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6T4P-4PYGVR7-3&_user=2460038&_coverDate=02%2F15%2F2008&_rdoc=5&_fmt=high&_orig=browse&_origin=browse&_zone=rslt_list_item&_srch=doc-info(%23toc%234980%232008%23999249995%23679515%23FLA%23display%23Volume)&_cdi=4980&_sort=d&_docanchor=&_ct=22&_acct=C000057398&_version=1&_urlVersion=0&_userid=2460038&md5=8bb5601e8c80c87e13c61b40ceaf158a&searchtype=a"> Full text</a> <br> <br>

Language: English

Type (Professor's evaluation): Scientific