LCT-3d Induces Oxidative Stress-Mediated Apoptosis by Upregulating Death Receptor 5 in Gastric Cancer Cells
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-Caspas...
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| Format: | Article |
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Frontiers Media S.A.
2021-04-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2021.658608/full |
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| author | Menglin Wang Xinxin Wu Lu Yu Zi-yun Hu Xiaobo Li Xia Meng Chun-tao Lv Gi-Young Kim Yung Hyun Choi Zhenya Wang Hai-Wei Xu Cheng-Yun Jin Cheng-Yun Jin |
| author_facet | Menglin Wang Xinxin Wu Lu Yu Zi-yun Hu Xiaobo Li Xia Meng Chun-tao Lv Gi-Young Kim Yung Hyun Choi Zhenya Wang Hai-Wei Xu Cheng-Yun Jin Cheng-Yun Jin |
| author_sort | Menglin Wang |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-e2a25caed06b43b4ab783e669b5d0c04 |
| institution | DOAJ |
| issn | 2234-943X |
| language | English |
| publishDate | 2021-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj-art-e2a25caed06b43b4ab783e669b5d0c042025-08-20T03:21:32ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2021-04-011110.3389/fonc.2021.658608658608LCT-3d Induces Oxidative Stress-Mediated Apoptosis by Upregulating Death Receptor 5 in Gastric Cancer CellsMenglin Wang0Xinxin Wu1Lu Yu2Zi-yun Hu3Xiaobo Li4Xia Meng5Chun-tao Lv6Gi-Young Kim7Yung Hyun Choi8Zhenya Wang9Hai-Wei Xu10Cheng-Yun Jin11Cheng-Yun Jin12Key Laboratory of Advanced Technology for Drug Preparation, Ministry of Education, School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, ChinaKey Laboratory of Advanced Technology for Drug Preparation, Ministry of Education, School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, ChinaKey Laboratory of Advanced Technology for Drug Preparation, Ministry of Education, School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, ChinaKey Laboratory of Advanced Technology for Drug Preparation, Ministry of Education, School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, ChinaKey Laboratory of Advanced Technology for Drug Preparation, Ministry of Education, School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, ChinaKey Laboratory of Advanced Technology for Drug Preparation, Ministry of Education, School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, ChinaKey Laboratory of Advanced Technology for Drug Preparation, Ministry of Education, School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, ChinaDepartment of Marine Life Sciences, Jeju National University, Jeju, South KoreaDepartment of Biochemistry, College of Oriental Medicine, Dong-Eui University, Busan, South KoreaKey Laboratory of Advanced Technology for Drug Preparation, Ministry of Education, School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, ChinaKey Laboratory of Advanced Technology for Drug Preparation, Ministry of Education, School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, ChinaKey Laboratory of Advanced Technology for Drug Preparation, Ministry of Education, School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, ChinaState Key Laboratory of Esophageal Cancer Prevention & Treatment, Zhengzhou University, Zhengzhou, ChinaGastric 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.https://www.frontiersin.org/articles/10.3389/fonc.2021.658608/fullLCT-3dDR5reactive oxygen speciesNrf2apoptosisgastric cancer |
| spellingShingle | Menglin Wang Xinxin Wu Lu Yu Zi-yun Hu Xiaobo Li Xia Meng Chun-tao Lv Gi-Young Kim Yung Hyun Choi Zhenya Wang Hai-Wei Xu Cheng-Yun Jin Cheng-Yun Jin LCT-3d Induces Oxidative Stress-Mediated Apoptosis by Upregulating Death Receptor 5 in Gastric Cancer Cells Frontiers in Oncology LCT-3d DR5 reactive oxygen species Nrf2 apoptosis gastric cancer |
| title | LCT-3d Induces Oxidative Stress-Mediated Apoptosis by Upregulating Death Receptor 5 in Gastric Cancer Cells |
| title_full | LCT-3d Induces Oxidative Stress-Mediated Apoptosis by Upregulating Death Receptor 5 in Gastric Cancer Cells |
| title_fullStr | LCT-3d Induces Oxidative Stress-Mediated Apoptosis by Upregulating Death Receptor 5 in Gastric Cancer Cells |
| title_full_unstemmed | LCT-3d Induces Oxidative Stress-Mediated Apoptosis by Upregulating Death Receptor 5 in Gastric Cancer Cells |
| title_short | LCT-3d Induces Oxidative Stress-Mediated Apoptosis by Upregulating Death Receptor 5 in Gastric Cancer Cells |
| title_sort | lct 3d induces oxidative stress mediated apoptosis by upregulating death receptor 5 in gastric cancer cells |
| topic | LCT-3d DR5 reactive oxygen species Nrf2 apoptosis gastric cancer |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2021.658608/full |
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