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http://ir.nhri.org.tw/handle/3990099045/2717
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| Title: | A novel bis-benzylidenecyclopentanone derivative, BPR0Y007, inducing a rapid caspase activation involving upregulation of Fas (CD95/APO-1) and wild-type p53 in human oral epidermoid carcinoma cells |
| Authors: | Juang, SH;Pan, WY;Kuo, CC;Liou, JP;Hung, YM;Chen, LT;Hsieh, HP;Chang, JY |
| Contributors: | National Institute of Cancer Research;Division of Biotechnology and Pharmaceutical Research |
| Abstract: | BPROY007, a bis-benzylidenecyclopentanone derivative (2,5-bis-(4-hydroxy-3-methoxybenzylidene) cyclopentanone), was identified in our laboratory as a novel antineoplastic agent with a broad spectrum of antitumor activity against many human cancer cells. A previous study showed that BPROY007 inhibited DNA topoisomerase I (Top 1) activity and prevented tubulin polymerization. Notably, no cross-resistance with BPROY007 was observed in camptothecin-, VP-16- or vincristine-resistant cell lines. In this study, we further investigated the cellular and molecular events underlying the antitumoral function of this compound in human oral epidermoid carcinoma KB cells, focusing on the early cytotoxic effect. Treatment of KB cells with BPROY007-induced G(2)/M phase arrest followed by sub-G, phase accumulation. Annexin-V-propidium iodide (PI) binding assay and DNA fragmentation assay further indicated that B PROY007-induced cell death proceeded through an apoptotic pathway as opposed to via necrosis. This compound produced a time-dependent activation of caspases-3 and -8, however, another caspase-3 initiator, caspase-9, was only marginally activated at later time point. We further demonstrated that the activation of the caspases cascade and nuclear fragmentation was not associated with inactivated Bcl-2 and perturbed mitochondrial membrane potential by BPROY007. The finding that BPROY007-induced apoptosis through a membrane-mediated mechanism was supported by up-regulated expression of Fas (CD95/APO-1), but not Fas-L. Furthermore, up-regulation of p53 and its affected gene, MDM2, in KB cells was found after BPROY007 exposure. Overall, our results demonstrated that the BPROY007 could induce an early cytotoxic apoptosis through a caspase-8-dependent but mitochondrial-caspase-9 independent pathway, and involving upregulation of p53. (C) 2004 Elsevier Inc. All rights reserved. |
| Keywords: | Pharmacology & Pharmacy |
| Date: | 2004-07-15 |
| Relation: | Biochemical Pharmacology. 2004 Jul;68(2):293-303. |
| Link to: | http://dx.doi.org/10.1016/j.bcp.2004.03.036 |
| JIF/Ranking 2023: | http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0006-2952&DestApp=IC2JCR |
| Cited Times(WOS): | https://www.webofscience.com/wos/woscc/full-record/WOS:000222308200010 |
| Cited Times(Scopus): | http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=2942573028 |
| Appears in Collections: | [張俊彥] 期刊論文
[謝興邦] 期刊論文
[莊聲宏(1997-2004)] 期刊論文
[郭靜娟] 期刊論文
[陳立宗] 期刊論文
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| 000222308200010.pdf | | 432Kb | Adobe PDF | 1092 | View/Open |
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