國家衛生研究院 NHRI:Item 3990099045/9775

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Please use this identifier to cite or link to this item: http://ir.nhri.org.tw/handle/3990099045/9775

Title:	HQO-0601, an amide-containg 3, 4-dihydroquinolinone derivative, against human hematologic malignancies through inhibition of mammalian target of repamycin signaling pathway
Authors:	Juang, SH;Yang, YC;Lee, CH;Lin, YC;Kuo, CC;Wang, TC
Contributors:	National Institute of Cancer Research
Abstract:	Recently, the hydroxycoumarine skeleton of flavonols has been demonstrated to have a variety of biological activities including antioxidant properties and the ability to induce apoptosis. As a result, they have become the focus of intense studies aimed at developing novel compounds with pharmacological applications. Accordingly, we are interested in designing and synthesizing a series of amide-containing 3, 4-didhydroquinolinones (HQO) derivatives as novel hydroxycoumarine analogues and to evaluate their anti-cancer activities for further drug development. Of over sixty derivatives we tested, several amide substitute compounds showed excellent antiproliferative activity towards human nasopharyngeal carcinoma (NPC-TW01), lung carcinoma (H661), and leukemia (Jurkat) cells. Among them, HQO-0601 possesses great potency towards Jurkat cells with an IC50 of around 200 nM compared to the micromolar range of HQO-0601 needed for NPC-TW01 and H661 cells. In order to distinguish whether the antiproliferative effect of HQO-0601 is cell-line specific or tissue-specific, several human leukemia, solid tumors cells and peripheral blood mononuclear cells (PBMCs) were evaluated. Our results showed that leukemia cell lines are more sensitive to HQO-0601 treatment than solid tumor cell lines. Further examination also showed that HQO-0601 is not cytotoxic to PBMCs even at 50 \#956;M of HQO-0601, the highest concentration used. Further results indicated that HQO-0601 induces growth retardation at S-phase was accompanied by a marked decrease in the level of phosphorylation of CDK2 without affecting the CDK2 and cyclin A protein expression. Moreover, HQO-0601 treatment significantly alters the phosphorylation status of AKT and the mTOR effectors p70 S6 kinase. Taken together, our results strongly indicated that the HQO-0601 induced cell arrest of leukemia might involve in interrupting of the AKT/mTOR signaling pathway and merits further detailed studies.
Date:	2009-05
Relation:	Cancer Research. 2009 May;69:Abstract number LB-51.
Link to:	http://cancerres.aacrjournals.org/content/69/9_Supplement/LB-51.short
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:000209702705033
Appears in Collections:	[Ching-Chuan Kuo] Conference Papers/Meeting Abstract [Shin-Hun P. Juang(1997-2004)] Conference Papers/Meeting Abstract

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