2,3-二羟基-9,10-蒽醌的体外抗增殖活性通过细胞色素c释放的半胱天冬酶介导途径，伴随PI3K/AKT和COX-2抑制，诱导COLO320细胞凋亡。
In vitro antiproliferative activity of 2,3-dihydroxy-9,10-anthraquinone induced apoptosis against COLO320 cells through cytochrome c release caspase mediated pathway with PI3K/AKT and COX-2 inhibition.
作者信息
Balachandran C, Emi N, Arun Y, Yamamoto N, Duraipandiyan V, Inaguma Yoko, Okamoto Akinao, Ignacimuthu S, Al-Dhabi N A, Perumal P T
机构信息
Department of Hematology, Fujita Health University, 1-98, Dengakugakubo, Kutsukake-cho, Toyoake, Aichi, 470-1192, Japan; Division of Cancer Biology, Entomology Research Institute, Loyola College, Chennai, 600 034, India.
Department of Hematology, Fujita Health University, 1-98, Dengakugakubo, Kutsukake-cho, Toyoake, Aichi, 470-1192, Japan.
出版信息
Chem Biol Interact. 2016 Apr 5;249:23-35. doi: 10.1016/j.cbi.2016.02.016. Epub 2016 Feb 23.
The present study investigated the anticancer activity of 2,3-dihydroxy-9,10-anthraquinone against different cancer cells such as MCF-7, COLO320, HepG-2, Skov-3, MOLM-14, NB-4, CEM, K562, Jurkat, HL-60, U937, IM-9 and Vero. 2,3-dihydroxy-9,10-anthraquinone showed good antiproliferative activity against COLO320 cells when compared to other tested cells. The cytotoxicity results showed 79.8% activity at the dose of 2.07 μM with IC50 value of 0.13 μM at 24 h in COLO320 cells. So we chose COLO320 cells for further anticancer studies. mRNA expression was confirmed by qPCR analysis using SYBR green method. Treatment with 2,3-dihydroxy-9,10-anthraquinone was found to trigger intrinsic apoptotic pathway as indicated by down regulation of Bcl-2, Bcl-xl; up regulation of Bim, Bax, Bad; release of cytochrome c and pro-caspases cleaving to caspases. Furthermore, 2,3-dihydroxy-9,10-anthraquinone stopped at G0/G1 phase with modulation in protein levels of cyclins. On the other hand PI3K/AKT signaling plays an important role in cell metabolism. We found that 2,3-dihydroxy-9,10-anthraquinone inhibits PI3K/AKT activity after treatment. Also, COX-2 enzyme plays a major role in colorectal cancer. Our results showed that the treatment significantly reduced COX-2 enzyme in COLO320 cells. These results indicated antiproliferative activity of 2,3-dihydroxy-9,10-anthraquinone involving apoptotic pathways, mitochondrial functions, cell cycle checkpoint and controlling the over expression genes during the colorectal cancer. Molecular docking studies showed that the compound bound stably to the active sites of Bcl-2, COX-2, PI3K and AKT. This is the first report of anticancer mechanism involving 2,3-dihydroxy-9,10-anthraquinone in COLO320 cells. The present results might provide helpful suggestions for the design of antitumor drugs toward colorectal cancer treatment.
本研究调查了2,3 - 二羟基 - 9,10 - 蒽醌对不同癌细胞的抗癌活性，这些癌细胞包括MCF - 7、COLO320、HepG - 2、Skov - 3、MOLM - 14、NB - 4、CEM、K562、Jurkat、HL - 60、U937、IM - 9和Vero。与其他受试细胞相比，2,3 - 二羟基 - 9,10 - 蒽醌对COLO320细胞表现出良好的抗增殖活性。细胞毒性结果显示，在24小时时，剂量为2.07 μM时活性为79.8%，COLO320细胞的IC50值为0.13 μM。因此，我们选择COLO320细胞进行进一步的抗癌研究。使用SYBR绿法通过qPCR分析确认mRNA表达。发现用2,3 - 二羟基 - 9,10 - 蒽醌处理可触发内源性凋亡途径，表现为Bcl - 2、Bcl - xl下调；Bim、Bax、Bad上调；细胞色素c释放以及前半胱天冬酶裂解为半胱天冬酶。此外，2,3 - 二羟基 - 9,10 - 蒽醌使细胞停滞在G0/G1期，同时细胞周期蛋白的蛋白质水平发生变化。另一方面，PI3K/AKT信号通路在细胞代谢中起重要作用。我们发现，处理后2,3 - 二羟基 - 9,10 - 蒽醌抑制PI3K/AKT活性。此外，COX - 2酶在结直肠癌中起主要作用。我们的结果表明，该处理显著降低了COLO320细胞中的COX - 2酶。这些结果表明2,3 - 二羟基 - 9,10 - 蒽醌的抗增殖活性涉及凋亡途径、线粒体功能、细胞周期检查点以及在结直肠癌期间控制过表达基因。分子对接研究表明，该化合物与Bcl - 2、COX -
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