Isorhamnetin augments the anti-tumor effect of capeciatbine through the negative regulation of NF-κB signaling cascade in gastric cancer

被引:160
作者
Manu, Kanjoormana A. [1 ]
Shanmugam, Muthu K. [1 ]
Ramachandran, Lalitha [1 ]
Li, Feng [1 ]
Siveen, Kodappully Sivaraman [1 ]
Chinnathambi, Arunachalam [2 ]
Zayed, M. E. [2 ]
Alharbi, Sulaiman Ali [2 ]
Arfuso, Frank [3 ]
Kumar, Alan Prem [1 ,3 ,4 ,5 ]
Ahn, Kwang Seok [6 ]
Sethi, Gautam [1 ,2 ,3 ]
机构
[1] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Pharmacol, Singapore 117597, Singapore
[2] King Saud Univ, Dept Bot & Microbiol, Coll Sci, Riyadh 11451, Saudi Arabia
[3] Curtin Univ, Curtin Hlth Innovat Res Inst, Sch Biomed Sci, Fac Hlth Sci,Biosci Res Precinct, Perth, WA 6845, Australia
[4] Ctr Translat Med, Canc Sci Inst Singapore, Singapore 117599, Singapore
[5] Univ N Texas, Dept Biol Sci, Denton, TX 76203 USA
[6] Kyung Hee Univ, Coll Korean Med, Seoul 130701, South Korea
关键词
Gastric cancer; Isorhamnetin; Capecitabine; NF-kappa B; APOPTOSIS; CHEMOTHERAPY; MODULATION; ACTIVATION; GROWTH; PROLIFERATION; CAPECITABINE; INFLAMMATION; XENOGRAFT; BLOCKING;
D O I
10.1016/j.canlet.2015.03.033
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Development of drug resistance to standard chemotherapy is a common phenomenon that leads to poor prognosis in patients. Thus, novel agents that can attenuate chemoresistance are urgently needed. Therefore, we analyzed whether isorhamnetin (IH), a 3'-O-methylated metabolite of quercetin, can enhance the potential efficacy of capecitabine in gastric cancer. The potential effect of IH on viability was analyzed by MTT assay, apoptosis by flow cytometric analysis, and NF-kappa B activation by DNA binding as well as Western blot assays. The in vivo effect of IH was also examined on the growth of subcutaneously implanted tumors in nude mice. IH inhibited the viability, potentiated the apoptotic effects of capecitabine, abrogated NF-kappa B activation, and suppressed the expression of various NF-kappa B regulated gene products in tumor cells. In a gastric cancer xenograft model, administration of IH alone (1 mg/kg body weight, i.p.) significantly suppressed the tumor growth alone as well as in combination with capecitabine. IH further reduced NF-kappa B activation and the expression of various proliferative and oncogenic biomarkers in tumor tissues. Overall, our results demonstrate that IH can significantly enhance the anti-tumor effects of capecitabine through the negative regulation of NF-kappa B regulated oncogenic genes. (C) 2015 Elsevier Ireland Ltd. All rights reserved.
引用
收藏
页码:28 / 36
页数:9
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