Sanggenon C induces apoptosis of colon cancer cells via inhibition of NO production, iNOS expression and ROS activation of the mitochondrial pathway.

Sanggenon C induces apoptosis of colon cancer cells via inhibition of NO production, iNOS expression and ROS activation of the mitochondrial pathway.
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DOI:
10.3892/or.2017.5912
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发表时间:
2017-10
期刊:
影响因子:
4.2
通讯作者:
Wang CF
Wang CF
中科院分区:
医学3区
文献类型:
--
作者:
Chen LD;Liu ZH;Zhang LF;Yao JN;Wang CF

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Sanggenon C是苯并吡喃酮类黄酮衍生物的一种众所周知的主要活性剂,具有有价值的生物学特性,包括抗癌、抗炎、抗微生物、抗病毒、抗血栓形成和免疫调节活性。在这项研究中,我们调查的分子机制,其中sanggenon C介导的诱导结直肠癌细胞(CRC)的细胞死亡。用sanggenon C(0、5、10、20、40和80 μM)处理结肠直肠癌细胞(LoVo、HT-29和SW 480)导致结肠癌细胞增殖受到抑制。此外,Sanggenon C(10、20、40 µM)可诱导HT-29结肠癌细胞凋亡以及增加ROS生成。此外,sanggenon C处理增加细胞内Ca ~(2+)和ATP水平,同时通过抑制诱导型一氧化氮合酶的表达来抑制一氧化氮的产生。这导致线粒体凋亡途径的激活,如Bcl-2蛋白表达的降低所证明的。因此,在体内进一步证实了桑根酮C对结肠移植瘤的抗生长和促凋亡作用。总的来说,我们的研究结果表明,sanggenon C诱导结肠癌细胞凋亡的活性氧产生增加,减少一氧化氮的产生,这是与诱导型一氧化氮合酶的表达抑制和线粒体凋亡途径的激活。
Sanggenon C is a well-known, major active agent of the flavonoid derivative of benzopyrone with valuable biological properties, including anticancer, anti-inflammatory, antimicrobial, antiviral, antithrombotic, and immune-modulatory activities. In this study, we investigated the molecular mechanisms by which sanggenon C mediated the induction of cell death in colorectal cancer cells (CRC). Treatment of colorectal cancer cells (LoVo, HT-29 and SW480) with sanggenon C (0, 5, 10, 20, 40 and 80 µM) resulted in inhibited proliferation of colon cancer cells. In addition, Sanggenon C (10, 20, 40 µM) induces apoptosis of HT-29 colon cancer cells as well as the increased ROS generation. Furthermore, treatment with sanggenon C increased the level of intracellular Ca2+ and ATP, while inhibited the nitric oxide production via inhibiting inducible nitric oxide synthase expression. This resulted in the activation of mitochondrial apoptosis pathway as evidenced by the decrease in Bcl-2 protein expression. Consistently, the anti-growth and pro-apoptosis effects of sanggenon C on xenograft colon tumor were further confirmed in vivo. Collectively, our results demonstrated sanggenon C induced apoptosis of colon cancer cells by increased reactive oxygen species generation and decreased nitric oxide production, which is associated with inhibition of inducible nitric oxide synthase expression and activation of mitochondrial apoptosis pathway.
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