LCT-3d Induces Oxidative Stress-Mediated Apoptosis by Upregulating Death Receptor 5 in Gastric Cancer Cells.
LCT-3d Induces Oxidative Stress-Mediated Apoptosis by Upregulating Death Receptor 5 in Gastric Cancer Cells.
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DOI：
10.3389/fonc.2021.658608
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发表时间：
2021
影响因子：
4.7
通讯作者：
Jin CY
中科院分区：
文献类型：
--
作者：
Wang M;Wu X;Yu L;Hu ZY;Li X;Meng X;Lv CT;Kim GY;Choi YH;Wang Z;Xu HW;Jin CY
胃癌是一个全球性的健康问题。在这项研究中，我们研究了一种新的吲哚衍生物，称为LCT-3D，通过四甲基偶氮唑盐比色法研究了其抑制胃癌细胞生长的作用。Western blotting结果表明，LCT-3D可调控线粒体相关蛋白和切割Caspase3/9，从而诱导细胞凋亡。观察LCT-3D对MGC803细胞死亡受体5(DR5)表达的上调作用。敲除DR5基因可部分逆转LCT-3D诱导的线粒体凋亡。LCT-3D可使MGC803细胞内的ROS水平升高，并可被ROS抑制剂N-乙酰半胱氨酸(NAC)阻断。结果表明，ROS升高可上调DR5的表达，通过线粒体途径诱导细胞凋亡。尽管核因子红系2相关因子2(Nrf2)通路在保护胃癌细胞免受ROS损伤中发挥了重要作用，但它不能逆转LCT-3D诱导的细胞凋亡。综上所述，我们的研究表明，LCT-3D通过DR5介导的线粒体凋亡途径诱导胃癌细胞凋亡。LCT-3D可能是一种新的先导化合物，用于开发胃癌的抗癌活性。
Gastric cancer is a global health problem. In this study, we investigate the role of a novel Indole derivative, named LCT-3d, in inhibiting the growth of gastric cancer cells by MTT assay. The Western blotting results showed that LCT-3d modulated the mitochondrial-related proteins and Cleaved-Caspases 3/9, to induce cell apoptosis. The up-regulation of Death receptor 5 (DR5) in MGC803 cells was observed with LCT-3d treatment. Knockdown of DR5 on MGC803 cells partially reversed the LCT-3d-induced mitochondrial apoptosis. The level of Reactive Oxygen Species (ROS) in MGC803 cells was increased with LCT-3d treatment and could be blocked with the pretreatment of the ROS inhibitor N-Acetylcysteine (NAC). The results demonstrate that the elevating ROS can up-regulate the expression of DR5, resulting in apoptosis via mitochondrial pathway. Although the nuclear factor erythroid-2 related factor 2 (Nrf2) pathway served an important role in protecting gastric cancer cells against the injury of ROS, it can’t reverse LCT-3d-induced cell apoptosis. Taken together, our study showed that LCT-3d induced apoptosis via DR5-mediated mitochondrial apoptotic pathway in gastric cancer cells. LCT-3d could be a novel lead compound for development of anti-cancer activity in gastric cancer.
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影响因子：
4.7
作者：
Gao HL;Gupta P;Cui Q;Ashar YV;Wu ZX;Zeng L;Lei ZN;Teng QX;Ashby CR Jr;Guan Y;Chen ZS
通讯作者：
Chen ZS
影响因子：
2.7
作者：
Sadhu, M. Naveen;Sivanandhan, Dhanalakshmi;Rajagopal, Sridharan
通讯作者：
Rajagopal, Sridharan
影响因子：
5.2
作者：
Wang, Yi-Yue;Lee, Kyung-Tae;Choi, Jung-Hye
通讯作者：
Choi, Jung-Hye
影响因子：
2
作者：
Jin，Cheng-Yun;Molagoda，Ilandarage Menu Neelaka;Choi，Yung Hyun
通讯作者：
Choi，Yung Hyun
影响因子：
5.5
作者：
Lei ZN;Teng QX;Zhang W;Fan YF;Wang JQ;Cai CY;Lu KW;Yang DH;Wurpel JND;Chen ZS
通讯作者：
Chen ZS