Gen-27, a newly synthesized flavonoid, inhibits glycolysis and induces cell apoptosis via suppression of hexokinase II in human breast cancer cells
Gen-27, a newly synthesized flavonoid, inhibits glycolysis and induces cell apoptosis via suppression of hexokinase II in human breast cancer cells
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Gen-27 是一种新合成的类黄酮，通过抑制人乳腺癌细胞中的己糖激酶 II 来抑制糖酵解并诱导细胞凋亡
DOI：
10.1016/j.bcp.2016.11.001
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发表时间：
2017
影响因子：
5.8
通讯作者：
Hu Rong
中科院分区：
文献类型：
--
作者：
Tao Lei;Wei Libing;Liu Yishi;Ding Yang;Liu Xiuting;Zhang Xin;Wang Xiaoping;Yao Yuyuan;Lu Jinrong;Wang Qing;Hu Rong
我们以前曾报道，Gen-27，一种新合成的黄酮类化合物，对人结直肠癌细胞具有抗癌作用。在这项研究中，我们研究了人乳腺癌细胞系的抗癌作用及其机制。我们证明Gen-27以浓度和时间依赖性方式抑制人乳腺癌细胞的生长和增殖。Gen-27可诱导细胞凋亡，其特征为线粒体膜电位（Δ Km）降低、细胞色素（Cytc）从线粒体释放到胞浆、半胱氨酸天冬氨酸蛋白酶（caspase）激活和多聚腺苷二磷酸核糖聚合酶（PARP）的诱导。此外，Gen-27抑制了人类乳腺癌细胞中的糖酵解。Gen-27处理后，HKII的表达下调，同时HKII与VDAC的相互作用减弱。进一步的研究表明，线粒体凋亡的诱导与Gen-27降低HKII表达有关。最后，在体内研究表明，Gen-27显着抑制MDA-MB-231乳腺癌原位肿瘤的生长和促进细胞凋亡，具有低全身毒性。综上所述，结果表明Gen-27对人乳腺癌具有显著的抗癌作用，它可能被用作治疗乳腺癌的新型抗癌剂。
We have previously reported that Gen-27, a newly synthesized flavonoid, exhibits anticancer effects against human colorectal cancer cells. In this study, we investigated the anticancer effects in human breast cancer cell lines and its underlying mechanisms. We demonstrated that Gen-27 inhibited the growth and proliferation of human breast cancer cells in concentration and time-dependent manners. It was found that Gen-27 induced mitochondrial-mediated apoptosis, characterized by the dissipation of mitochondrial membrane potential (ΔΨm), cytochromec(Cytc) release from mitochondria to cytosol, activation of caspases and induction of poly (ADP-ribose) polymerase (PARP). In addition, Gen-27 inhibited the glycolysis in human breast cancer cells. After treatment with Gen-27, the expression of HKII was down-regulated, accompanied by weakened interaction of HKII and VDAC. Further research revealed that the induction of mitochondrial apoptosis was associated with the decrease of HKII expression by Gen-27. Finally,in vivostudies demonstrated that Gen-27 significantly suppressed the growth and promoted apoptosis of MDA-MB-231 breast cancer orthotopic tumors with low systemic toxicity. In conclusion, the results showed that Gen-27 had significant anticancer effects against human breast cancer and it may potentially be used as a novel anticancer agent for the treatment of breast cancer.