TEOA Promotes Autophagic Cell Death via ROS-Mediated Inhibition of mTOR/p70S6k Signaling Pathway in Pancreatic Cancer Cells

Yang, Chen; Li, Yanchun; Hu, Wanye; Wang, Xu; Hu, Jiayu; Yuan, Chen; Zhou, Chunhui; Wang, Hairui; Du, Jing; Wang, Ying; Tong, Xiangmin

doi:10.3389/fcell.2021.734818

Cited by 15 publications

(15 citation statements)

References 36 publications

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“…The clonogenic ability of cells was carried out according to our previous published paper [ 24 ]. The cells were collected and seeded on a 12-well plate with a density of 2,000 cells/well.…”

Section: Methodsmentioning

confidence: 99%

CDC25C is a prognostic biomarker and correlated with mitochondrial homeostasis in pancreatic adenocarcinoma

Zhou

Wang

et al. 2022

Bioengineered

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Pancreatic adenocarcinoma (PAAD) is a common digestive tract malignant tumor with an extremely poor prognosis. The survival and prognosis may significantly improve if it is diagnosed early. Therefore, identifying biomarkers for early diagnosis is still considered a great clinical challenge in PAAD. Cell Division Cycle 25C (CDC25C), a cardinal cell cycle regulatory protein, directly mediates the G2/M phase and is intimately implicated in tumor development. In the current study, we aim to explore the possible functions of CDC25C and determine the potential role of CDC25C in the early diagnosis and prognosis of PAAD. Expression analysis indicated that CDC25C was overexpressed in PAAD . In addition, survival analysis revealed a strong correlation between the enhanced expression of CDC25C and poor survival in PAAD. Furthermore, pathway analysis showed that CDC25C is related to TP53 signaling pathways, glutathione metabolism, and glycolysis. Mechanically, our in vitro experiments verified that CDC25C was capable of promoting cell viability and proliferation. CDC25C inhibition increases the accumulation of ROS, inhibits mitochondrial respiration, suppresses glycolysis metabolism and reduces GSH levels. To summarize, CDC25C may be involved in energy metabolism by maintaining mitochondrial homeostasis. Our results suggested that CDC25C is a potential biological marker and promising therapeutic target of PAAD.

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Section: Methodsmentioning

confidence: 99%

CDC25C is a prognostic biomarker and correlated with mitochondrial homeostasis in pancreatic adenocarcinoma

Zhou

Wang

et al. 2022

Bioengineered

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“…Recently, Yang et al demonstrated that this herbal inhibited the proliferation and migration of PC cells concurrently, causing the induction of mitochondrial dysfunction in PANC1 and SW1990 cells. Finally, TEOA induced autophagic cell death in PC cells by inactivating the ROS-dependent mTOR/p70S6k signaling pathway [168].…”

Section: Sugiolmentioning

confidence: 96%

Herbals and Plants in the Treatment of Pancreatic Cancer: A Systematic Review of Experimental and Clinical Studies

et al. 2022

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Background: Pancreatic cancer represents the most lethal malignancy among all digestive cancers. Despite the therapeutic advances achieved during recent years, the prognosis of this neoplasm remains disappointing. An enormous amount of experimental (mainly) and clinical research has recently emerged referring to the effectiveness of various plants administered either alone or in combination with chemotherapeutic agents. Apart from Asian countries, the use of these plants and herbals in the treatment of digestive cancer is also increasing in a number of Western countries as well. The aim of this study is to review the available literature regarding the efficacy of plants and herbals in pancreatic cancer. Methods: The authors have reviewed all the experimental and clinical studies published in Medline and Embase, up to June 2021. Results: More than 100 plants and herbals were thoroughly investigated. Favorable effects concerning the inhibition of cancer cell lines in the experimental studies and a favorable clinical outcome after combining various plants with established chemotherapeutic agents were observed. These herbals and plants exerted their activity against pancreatic cancer via a number of mechanisms. The number and severity of side-effects are generally of a mild degree. Conclusion: A quite high number of clinical and experimental studies confirmed the beneficial effect of many plants and herbals in pancreatic cancer. More large, double-blind clinical studies assessing these natural products, either alone or in combination with chemotherapeutic agents should be conducted.

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“…Additionally, autophagy is increasingly investigated as a molecular target for cancer therapy. Our recent study demonstrated that excess autophagy results in autophagic cell death ( 12 ). However, autophagy plays two roles in tumorigenesis and development.…”

Section: Introductionmentioning

confidence: 99%

Autophagy-related prognostic signature characterizes tumor microenvironment and predicts response to ferroptosis in gastric cancer

et al. 2022

Front. Oncol.

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BackgroundGastric cancer (GC) is an important disease and the fifth most common malignancy worldwide. Autophagy is an important process for the turnover of intracellular substances. Autophagy-related genes (ARGs) are crucial in cancer. Accumulating evidence indicates the clinicopathological significance of the tumor microenvironment (TME) in predicting prognosis and treatment efficacy.MethodsClinical and gene expression data of GC were obtained from The Cancer Genome Atlas and Gene Expression Omnibus databases. A total of 22 genes with differences in expression and prognosis were screened from 232 ARGs. Three autophagy patterns were identified using an unsupervised clustering algorithm and scored using principal component analysis to predict the value of autophagy in the prognosis of GC patients. Finally, the relationship between autophagy and ferroptosis was validated in gastric cancer cells.ResultsThe expression of ARGs showed obvious heterogeneity in GC patients. Three autophagy patterns were identified and used to predict the overall survival of GC patients. These three patterns were well-matched with the immunophenotype. Kyoto Encyclopedia of Genes and Genomes and Gene Ontology enrichment analyses showed that the biological functions of the three autophagy patterns were different. A scoring system was then set up to quantify the autophagy model and further evaluate the response of the patients to the immunotherapy. Patients with high autophagy scores had a more severe tumor mutation burden and better prognosis. High autophagy scores were accompanied by high microsatellite instability. Patients with high autophagy scores had significantly higher PD-L1 expression and increased survival. The experimental results confirmed that the expression of ferroptosis genes was positively correlated with the expression of autophagy genes in different autophagy clusters, and inhibition of autophagy dramatically reversed the decrease in ferroptotic cell death and lipid accumulation.ConclusionsAutophagy patterns are involved in TME diversity and complexity. Autophagy score can be used as an independent prognostic biomarker in GC patients and to predict the effect of immunotherapy and ferroptosis-based therapy. This might benefit individualized treatment for GC.

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TEOA Promotes Autophagic Cell Death via ROS-Mediated Inhibition of mTOR/p70S6k Signaling Pathway in Pancreatic Cancer Cells

Cited by 15 publications

References 36 publications

CDC25C is a prognostic biomarker and correlated with mitochondrial homeostasis in pancreatic adenocarcinoma

CDC25C is a prognostic biomarker and correlated with mitochondrial homeostasis in pancreatic adenocarcinoma

Herbals and Plants in the Treatment of Pancreatic Cancer: A Systematic Review of Experimental and Clinical Studies

Autophagy-related prognostic signature characterizes tumor microenvironment and predicts response to ferroptosis in gastric cancer

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