Targeting ROS-Mediated Crosstalk Between Autophagy and Apoptosis in Cancer

Gao, Lixia; Loveless, Jenni; Shay, Chloe; Teng, Yong

doi:10.1007/978-3-030-42667-5_1

Cited by 104 publications

(66 citation statements)

References 62 publications

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“…Additionally, through intracellular ROS level measurement (Fig. 6D), ectopic expression of MT1M significantly evaluated the ROS level, which may, in turn, cause the apoptosis of ESCC cells (Gao et al, 2020). Because SOD1 is the hub gene in the ROS signaling pathway, we next examined the SOD1 activity through a SOD1 activity assay and verified that SOD1 enzymatic activity was suppressed by MT1M re-expression (P < 0.05; Fig.…”

Section: Ectopic Expression Of Mt1m Inhibits Sod1/pi3k Signaling Pathwaymentioning

confidence: 84%

Metallothionein MT1M Suppresses Carcinogenesis of Esophageal Carcinoma Cells through Inhibition of the Epithelial-Mesenchymal Transition and the SOD1/PI3K Axis

Peng

et al. 2021

Molecules and Cells

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Metallothionein (MT1M) belongs to a family of cysteinerich cytosolic protein and has been reported to be a tumor suppressor gene in multiple cancers. However, its role in esophageal carcinoma carcinogenesis remains unclear. In this study, MT1M expression was correlated with tumor type, stage, drinking and smoking history, as well as patient survival. We also studied the regulation and biological function of MT1M in esophageal squamous cell carcinoma (ESCC). We have found that MT1M is significantly downregulated in ESCC tissues compared with adjacent non-cancer tissues. Furthermore, restoration of expression by treatment with the demethylation agent A + T showed that MT1M downregulation might be closely related to hypermethylation in its promoter region. Over-expression of MT1M in ESCC cells significantly altered cell morphology, induced apoptosis, and reduced colony formation, cell viability, migration and epithelial-mesenchymal transition. Moreover, based on reactive oxygen species (ROS) levels, a superoxide dismutase 1 (SOD1) activity assay and protein analysis, we verified that the tumor-suppressive function of MT1M was at least partially caused by its upregulation of ROS levels, downregulation of SOD1 activity and phosphorylation of the SOD1 downstream pathway PI3K/AKT. In conclusion, our results demonstrated that MT1M was a novel tumorsuppressor in ESCC and may be disrupted by promoter CpG methylation during esophageal carcinogenesis.

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Section: Ectopic Expression Of Mt1m Inhibits Sod1/pi3k Signaling Pathwaymentioning

confidence: 84%

Metallothionein MT1M Suppresses Carcinogenesis of Esophageal Carcinoma Cells through Inhibition of the Epithelial-Mesenchymal Transition and the SOD1/PI3K Axis

Peng

et al. 2021

Molecules and Cells

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“…The Δψ m of HCC827 cells were decreased by CHE significantly, leading to cell apoptosis ( Figure 5A ) ( 25 ). After treatment with CHE, intracellular ROS increased ( Figures 5B, C ), which can produce cytotoxicity by acting on proteins and damaging DNA and mediate the rapid apoptosis of cells ( 26 , 27 ).…”

Section: Resultsmentioning

confidence: 99%

Using Liposomes to Alleviate the Toxicity of Chelerythrine, a Natural PKC Inhibitor, in Treating Non-Small Cell Lung Cancer

et al. 2021

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Aim of the StudyCHE can inhibit the proliferation of lung cancer cells and induce apoptosis. However, despite having in vivo toxicity, CHE has not been thoroughly investigated in term of its in vivo antitumor effect. The present study evaluated the antitumor effect of CHE on non-small cell lung cancer cell line HCC827.MethodsThe antitumor effect of CHE on HCC827 was evaluated, and its potential work mechanism was investigated. CHE long circulation liposomes (CHELPs) modified with polyethylene glycol have been optimized and characterized by in vivo pharmacokinetic studies. A HCC827 xenograft model was developed on BALB/c nude mice for the assessment of the effects of CHE and CHELP.ResultsCHE might inhibit HCC827 growth through the ROS/PKC-ϵ/caspase 3 pathway and glycolysis. The optimized CHELP remained stable after storage for 10 days at 4°C and exhibited sustained drug release, showing approximately one-fifteenth of the in vivo clearance rate and 86 times the absorption concentration of free drug. While increasing the bioavailability of CHE, CHELP showed a good therapeutic effect on HCC827 tumor-bearing nude mice and reduced the toxicity of the free drug, improving the safety of CHE.ConclusionsCHE is a candidate drug for NSCLC, and liposomes are effective in alleviating the toxicity of CHE.

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“…However, an excessively high level of ROS may cause excessive oxidative stress and lead to cell death through apoptosis, autophagy and necrosis (42). Novel anticancer agents have been developed to generate ROS and trigger oxidative stress-induced tumor cell death (42,43). This finding suggests that ROS may play an important role in TPL-mediated autophagy induction in SKOV3/DDP cells.…”

Section: Discussionmentioning

confidence: 99%

Triptolide inhibits JAK2/STAT3 signaling and induces lethal autophagy through ROS generation in cisplatin‑resistant SKOV3/DDP ovarian cancer cells

Zhong

Cheng

et al. 2021

Oncol Rep

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Advanced and recurrent ovarian cancer has a poor prognosis and is frequently resistant to numerous therapeutics; thus, safe and effective drugs are needed to combat this disease. Previous studies have demonstrated that triptolide (TPL) exhibits anticancer and sensitization effects against cisplatin (DDP)-resistant ovarian cancer both in vitro and in vivo by inducing apoptosis; however, the involvement of autophagy induced by TPL in resistant ovarian carcinoma remains unclear. In the present study, the results revealed that TPL induced autophagy to facilitate SKOV3/DDP ovarian cancer cell death. The xenograft experiment revealed that the autophagy inhibitor CQ significantly reduced TPL-mediated chemosensitization and tumor growth inhibition. Mechanically, TPL-induced autophagy in SKOV3/DDP cells was associated with the induction of ROS generation and inhibition of the Janus kinase 2 (JAK2)/signal transducer and activator of transcription-3 (STAT3) pathway. The inhibitory effect of TPL on the JAK2/STAT3 pathway could be restored in the presence of the antioxidant NAC. Furthermore, it was further determined that TPL disrupted the interaction between Mcl-1 and Beclin1, which was prevented by the JAK2/STAT3 signaling activator IL-6. Overall, the present results revealed a novel molecular mechanism whereby TPL induced lethal autophagy through the ROS-JAK2/STAT3 signaling cascade in SKOV3/DDP cells. The present study has provided the groundwork for future application of TPL in the treatment of ovarian cancer.

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Targeting ROS-Mediated Crosstalk Between Autophagy and Apoptosis in Cancer

Cited by 104 publications

References 62 publications

Metallothionein MT1M Suppresses Carcinogenesis of Esophageal Carcinoma Cells through Inhibition of the Epithelial-Mesenchymal Transition and the SOD1/PI3K Axis

Metallothionein MT1M Suppresses Carcinogenesis of Esophageal Carcinoma Cells through Inhibition of the Epithelial-Mesenchymal Transition and the SOD1/PI3K Axis

Using Liposomes to Alleviate the Toxicity of Chelerythrine, a Natural PKC Inhibitor, in Treating Non-Small Cell Lung Cancer

Triptolide inhibits JAK2/STAT3 signaling and induces lethal autophagy through ROS generation in cisplatin‑resistant SKOV3/DDP ovarian cancer cells

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