TRPV1 Antagonist DWP05195 Induces ER Stress-Dependent Apoptosis through the ROS-p38-CHOP Pathway in Human Ovarian Cancer Cells

Wang, Yiyue; Lee, Kyung Tae; Lim, Myong Cheol; Choi, Jung‐Hye

doi:10.3390/cancers12061702

Cited by 21 publications

(12 citation statements)

References 61 publications

(79 reference statements)

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“…These results suggested that NAC blocked the effect of ROS on gastric cancer cells, indicating that ROS triggered cell death through DR5-mediated mitochondrial apoptosis pathway (31). ROS are the key molecules in the process of apoptosis (32,33). It is reported that moderate level of ROS can increase the ability of cell survival (34).…”

Section: Discussionmentioning

confidence: 88%

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: 88%

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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“…As for the mechanisms of ROS or ER stress induced JNK activation, many research articles reported that ROS induced ER stress, which has been popularly accepted 47‐49 . Previously, we tested the survival of pancreatic beta cell (MIN6 cells) in response to TG (ER stress inducer) or H 2 O 2 (a ROS molecule) and by comparison we found H 2 O 2 resulted in apoptosis in a shorter time duration compared with TG 4,5 .…”

Section: Discussionmentioning

confidence: 94%

NR4A1 counteracts JNK activation incurred by ER stress or ROS in pancreatic β‐cells for protection

Liu

Mouguegue

et al. 2020

J Cellular Molecular Medi

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Although the aetiology of type 2 diabetes is complex, it is well accepted that insulin resistance leads to sustained hyperglycaemia or hyperlipidaemia, which consequently results in cellular ER stress and/ or ROS overproduction in pancreatic β-cells, whereas ER stress or ROS causes cell damage or even apoptosis. 1-6 Pancreatic β-cell loss plays an important role in the pathogenesis of type 2 diabetes. To reveal the

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“…In order to further confirm whether ERS is activated, CHOP was tested by western blot as a downstream gene of ERS. CHOP plays a role of convergent in ERS and controls the expression of stress‐induced genes related to apoptosis (Wang, Lee, et al, 2020). We also found that the expression level of CHOP increased in rat testis tissue.…”

Section: Discussionmentioning

confidence: 99%

Grape seed proanthocyanidin extract ameliorates cisplatin‐induced testicular apoptosis via PI3K/Akt/mTOR and endoplasmic reticulum stress pathways in rats

et al. 2021

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Testicular toxicity is an adverse reaction of the effective chemotherapy drug cisplatin (CIS). Our previous study found that grape seed proanthocyanidin extract (GSPE) had a protective effect on CIS‐induced testicular toxicity. However, the protective mechanism of GSPE against CIS‐induced testicular toxicity remains unknown. In this study, we aimed to investigate whether GSPE can reduce CIS‐induced testicular toxicity and its potential mechanism in rats. The results showed that GSPE ameliorated CIS‐induced the apoptosis of testicular cells and inhibited the protein levels of Bad, Cyt c, caspase‐9, caspase‐3, caspase‐12, GRP78, CHOP, IRE1α, p‐IRE1α, XBP‐1S, PERK, p‐PERK, eIF2α, and p‐eIF2α. Besides, GSPE reversed the downregulation of PI3K, p‐PI3K, Akt, p‐Akt, mTOR, and p‐mTOR protein expression induced by CIS. These results indicated that GSPE can improve CIS‐induced testicular cells apoptosis via activating PI3K/Akt/mTOR and inhibiting Bad/Cyt c/caspase‐9/caspase‐3 pathways. And GSPE relieved endoplasmic reticulum stress‐mediated apoptosis via inhibiting PREK/eIF2α and IRE1α/XBP‐1S/caspase‐12 pathways. In conclusion, the evidence suggested that GSPE can act as a protective agent against testicular toxicity induced by CIS. Practical applications Testicular toxicity was a well‐known adverse effect of cisplatin (CIS) in cancer treatment. Grape seed proanthocyanidin extract (GSPE) has been reported to serve as one of the most therapeutic potentials agents. In present study, we explored the regulatory effects of GSPE on the apoptosis induced by CIS, which involved testicular apoptosis mechanisms in rats. Our results indicated that CIS caused testicular toxicity via PI3K/AKT/mTOR and ERS mediated apoptosis pathway in rats. This toxicity was attenuated by GSPE treatment via activated PI3K/Akt/mTOR pathway, and inhibiting Bad/CytC/caspase‐9/caspase‐3 as well as PREK/eIF2α, IRE1α/XBP‐1S/caspase‐12 pathways. Our findings suggest that GSPE may be a novel protective agent against testicular toxicity induced by CIS.

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TRPV1 Antagonist DWP05195 Induces ER Stress-Dependent Apoptosis through the ROS-p38-CHOP Pathway in Human Ovarian Cancer Cells

Cited by 21 publications

References 61 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

NR4A1 counteracts JNK activation incurred by ER stress or ROS in pancreatic β‐cells for protection

Grape seed proanthocyanidin extract ameliorates cisplatin‐induced testicular apoptosis via PI3K/Akt/mTOR and endoplasmic reticulum stress pathways in rats

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