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LCT-3d Induces Oxidative Stress-Mediated Apoptosis by Upregulating Death Receptor 5 in Gastric Cancer Cells.

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العنوان: LCT-3d Induces Oxidative Stress-Mediated Apoptosis by Upregulating Death Receptor 5 in Gastric Cancer Cells.
المؤلفون: Wang M; Key Laboratory of Advanced Technology for Drug Preparation, Ministry of Education, School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, China., Wu X; Key Laboratory of Advanced Technology for Drug Preparation, Ministry of Education, School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, China., Yu L; Key Laboratory of Advanced Technology for Drug Preparation, Ministry of Education, School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, China., Hu ZY; Key Laboratory of Advanced Technology for Drug Preparation, Ministry of Education, School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, China., Li X; Key Laboratory of Advanced Technology for Drug Preparation, Ministry of Education, School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, China., Meng X; Key Laboratory of Advanced Technology for Drug Preparation, Ministry of Education, School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, China., Lv CT; Key Laboratory of Advanced Technology for Drug Preparation, Ministry of Education, School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, China., Kim GY; Department of Marine Life Sciences, Jeju National University, Jeju, South Korea., Choi YH; Department of Biochemistry, College of Oriental Medicine, Dong-Eui University, Busan, South Korea., Wang Z; Key Laboratory of Advanced Technology for Drug Preparation, Ministry of Education, School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, China., Xu HW; Key Laboratory of Advanced Technology for Drug Preparation, Ministry of Education, School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, China., Jin CY; Key Laboratory of Advanced Technology for Drug Preparation, Ministry of Education, School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, China.; State Key Laboratory of Esophageal Cancer Prevention & Treatment, Zhengzhou University, Zhengzhou, China.
المصدر: Frontiers in oncology [Front Oncol] 2021 Apr 16; Vol. 11, pp. 658608. Date of Electronic Publication: 2021 Apr 16 (Print Publication: 2021).
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Frontiers Research Foundation] Country of Publication: Switzerland NLM ID: 101568867 Publication Model: eCollection Cited Medium: Print ISSN: 2234-943X (Print) Linking ISSN: 2234943X NLM ISO Abbreviation: Front Oncol Subsets: PubMed not MEDLINE
أسماء مطبوعة: Original Publication: [Lausanne : Frontiers Research Foundation]
مستخلص: 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.
Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer JH declared a shared affiliation with one of the authors, G-YK, to the handling editor at time of review.
(Copyright © 2021 Wang, Wu, Yu, Hu, Li, Meng, Lv, Kim, Choi, Wang, Xu and Jin.)
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فهرسة مساهمة: Keywords: DR5; LCT-3d; Nrf2; apoptosis; gastric cancer; reactive oxygen species
تواريخ الأحداث: Date Created: 20210503 Latest Revision: 20210504
رمز التحديث: 20221213
مُعرف محوري في PubMed: PMC8085419
DOI: 10.3389/fonc.2021.658608
PMID: 33937072
قاعدة البيانات: MEDLINE
الوصف
تدمد:2234-943X
DOI:10.3389/fonc.2021.658608