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Please use this identifier to cite or link to this item:
http://ir.nhri.org.tw/handle/3990099045/2719
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| Title: | BPR0L075, a novel synthetic indole compound with antimitotic activity in human cancer cells, exerts effective antitumoral activity in vivo |
| Authors: | Kuo, CC;Hsieh, HP;Pan, WY;Chen, CP;Lion, JP;Lee, SJ;Chang, YL;Chen, LT;Chen, CT;Chang, JY |
| Contributors: | National Institute of Cancer Research;Division of Biotechnology and Pharmaceutical Research |
| Abstract: | BPR0L075 is a novel synthetic compound discovered through research to identify new microtubule inhibitors. BPR0L075 inhibits tubulin polymerization through binding to the colchicine-binding site of tubulin. Cytotoxic activity of BPR0L075 in a variety of human tumor cell lines has been ascertained, with IC50 values in single-digit nanomolar ranges. As determined by flow cytometry, human cervical carcinoma KB cells are arrested in G(2)-M phases in a time-dependent manner before cell death occurs. Terminal deoxynucleotidyl transferase-mediated nick end labeling assay indicates that cell death proceeds through an apoptotic pathway. Additional studies indicate that the effect of BPR0L075 on cell cycle arrest is associated with an increase in cyclin B1 levels and a mobility shift of Cdc2 and Cdc25C. The changes in Cdc2 and Cdc25C coincide with the appearance of phosphoepitopes recognized by a marker of mitosis, MPM-2. Furthermore, phosphorylated forms of Bcl-2, perturbed mitochondrial membrane potential, and activation of the caspase-3 cascade may be involved in BPR0L075-induced apoptosis. Notably, several KB-derived multidrug-resistant cell lines overexpressing P-gp170/MDR and MRP are resistant to vincristine, paclitaxel, and colchicine but not to BPR0L075. Moreover, BPR0L075 shows potent activity against the growth of xenograft tumors of the gastric carcinoma MKN-45, human cervical carcinoma KB, and KB-derived P-gp170/MDR-overexpressing KB-VIN10 cells at i.v. doses of 50 mg/kg in nude mice. These findings indicate BPR0L075 is a promising anticancer compound with antimitotic activity that has potential for management of various malignancies, particularly for patients with drug resistance. |
| Keywords: | Oncology |
| Date: | 2004-07-01 |
| Relation: | Cancer Research. 2004 Jul;64(13):4621-4628. |
| Link to: | http://dx.doi.org/10.1158/0008-5472.CAN-03-3474 |
| JIF/Ranking 2023: | http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0008-5472&DestApp=IC2JCR |
| Cited Times(WOS): | https://www.webofscience.com/wos/woscc/full-record/WOS:000222407300032 |
| Cited Times(Scopus): | http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=3042740981 |
| Appears in Collections: | [張俊彥] 期刊論文
[李秀珠] 期刊論文
[謝興邦] 期刊論文
[陳炯東] 期刊論文
[郭靜娟] 期刊論文
[陳立宗] 期刊論文
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| 000222407300032.pdf | | 427Kb | Adobe PDF | 455 | View/Open |
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