XP-16, a new xanthono-pyridine derivative, induces apoptosis in human lung carcinoma A549 cells
10.3969/j.issn.1001-1978.2014.06.022
- VernacularTitle:呫吨酮并吡啶衍生物XP-16诱导人肺癌A549细胞凋亡
- Author:
Zhikai DAI
;
Chengfang YANG
;
Yifei CHEN
;
Junnan JIANG
;
Guanhua CHE
;
Jiangke QIN
- Publication Type:Journal Article
- Keywords:
N,N'-(7-oxo-7H-chromeno[3,2-h]quin-oline-5,9-diyl )-bis ( 2-( pyrrolidin-1-yl ) acetamide );
human lung carcinoma cell line A549;
mitochondria membrane potential;
apoptosis;
metallothionein 1 A;
intracelluar calcium
- From:
Chinese Pharmacological Bulletin
2014;(6):838-842
- CountryChina
- Language:Chinese
-
Abstract:
Aim To investigate the anticancer effect of a new xanthono-pyridine derivative N, N '-( 7-oxo-7H-chromeno[3,2-h] quinoline-5,9-diyl)-bis(2-( pyrroli-din-1-yl)acetamide) (XP-16) on human lung carcino-ma cell line A549 and the potential mechanism. Meth-ods Antiproliferative effect of XP-16 on A549 cells was evaluated by MTT assay, morphological examina-tion and colonial assay. Apoptosis detection was car-ried out using Hoechst 33258 and PI double-dyeing method. Intracellular Ca2+ concentration ( [ Ca2+] i ) and mitochondria membrane potential were detected by fluorospectrophotometer. A549 cells treated with XP-16 were collected for Bad and metallothionein 1 A ( MT-1 A ) transcript analysis by real-time reverse tran-scriptase-polymerase chain reaction ( qRT-PCR) . Re-sults XP-16 inhibited A549 cell proliferation in dose-and time-dependent manner. Typical apoptotic mor-
phology such as chromatin aggregation and nuclear fragmentation was observed in A549 cells treated with XP-16 for 24 h, and the apoptosis was showed in a dose-dependent manner. After treated with XP-16, [ Ca2+] i and mitochondria membrane potential of A549 cells were decreased, and relative mRNA level of Bad and MT-1A was up-regulated. Conclusions XP-16 has anticancer effect on A549 cells through apoptosis, which might be associated with decreasing intracellular Ca2+ concentration and mitochondria membrane poten-tial. Up-regulation of MT-1A expression might be the result of decreased [ Ca2+] i .
