Molecular mechanisms underlying the effects of the small molecule AMC-04 on apoptosis: Roles of the activating transcription factor 4-C/EBP homologous protein-death receptor 5 pathway

Kim, So Young; Hwang, Supyong; Choi, Min Kyung; Park, Sojung; Nam, Ky Youb; Kim, Inki

doi:10.1016/j.cbi.2020.109277

Cited by 10 publications

(4 citation statements)

References 38 publications

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“…A novel Indole derivative LCT-3d was found to induce apoptosis in gastric cancer cells through DR5-mediated mitochondrial apoptotic pathway (13,31). LCT-3d modulated the Bcl-2 family proteins and Cleaved-Caspases 3/9, and resulted in cell apoptosis in MGC803 and HGC27 cells.…”

Section: Discussionmentioning

confidence: 99%

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

Wang

Wu²,

Yu³

et al. 2021

Front. Oncol.

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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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Section: Discussionmentioning

confidence: 99%

“…In the previous work, we synthesized a potent Lysine (K)-Specific Demethylase 1A (LSD1) inhibitor, named LCT-9e (Figure 1B), which effectively inhibits the macrophages (THP-1 cells) growth (13). LCT-9e is the first irreversible LSD1 inhibitor, which is not derived from monoamine oxidase inhibitors.…”

Section: Introductionmentioning

confidence: 99%

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

Wang

Wu²,

Yu³

et al. 2021

Front. Oncol.

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“…p38 MAPK activation promotes inflammation by activating several pathways, such as the UPR PERK/EIF2α/ATF4 pathway ( Kim et al, 2020 ). In fact, trazodone reduced the UPR effector ATF4 in the cortex of rTg4510 mice without affecting the upstream UPR-dependent event, as shown in the hippocampus ( Halliday et al, 2017 ).…”

Section: Discussionmentioning

confidence: 99%

Improved Sleep, Memory, and Cellular Pathological Features of Tauopathy, Including the NLRP3 Inflammasome, after Chronic Administration of Trazodone in rTg4510 Mice

et al. 2022

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“…Also, Shapiro et al reported that ERα biomodulator BHPI induces persistent ERα-dependent PERK activation which promotes apoptosis and necrosis in endocrine-resistant BC cells [ 65 ]. Inki Kim et al found a new piperazine oxalate derivate (AMC-04) that induces apoptosis via activation of the ATF4/CHOP/DR5 pathway [ 66 ].…”

Section: Drugs Targeting Ers-associated Signaling Pathways In Bcmentioning

confidence: 99%

Endoplasmic reticulum stress targeted therapy for breast cancer

Liu

Liang

et al. 2022

Cell Commun Signal

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Recurrence, metastasis, and drug resistance are still big challenges in breast cancer therapy. Internal and external stresses have been proven to substantially facilitate breast cancer progression through molecular and systemic mechanisms. For example, endoplasmic reticulum stress (ERS) results in activation of the unfolded protein response (UPR), which are considered an important cellular stress response. More and more reports indicate its key role in protein homeostasis and other diverse functions involved in the process of breast cancer progression. Therefore, therapies targeting the activation of ERS and its downstream signaling pathways are potentially helpful and novel tools to counteract and fight breast cancer. However, recent advances in our understanding of ERS are focused on characterizing and modulating ERS between healthy and disease states, and so little attention has been paid to studying the role and clinical application of targeting ERS in a certain cancer. In this review, we summarize the function and main mechanisms of ERS in different molecular types of breast cancer, and focus on the development of agents targeting ERS to provide new treatment strategies for breast cancer.

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Molecular mechanisms underlying the effects of the small molecule AMC-04 on apoptosis: Roles of the activating transcription factor 4-C/EBP homologous protein-death receptor 5 pathway

Cited by 10 publications

References 38 publications

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

Improved Sleep, Memory, and Cellular Pathological Features of Tauopathy, Including the NLRP3 Inflammasome, after Chronic Administration of Trazodone in rTg4510 Mice

Endoplasmic reticulum stress targeted therapy for breast cancer

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