Discovery of novel akt1 inhibitor induces autophagy associated death in hepatocellular carcinoma cells

Meng, Yan; Zeng, Minghui; Pan, Zhaoping; Wu, Fengbo; Guo, Li; He, Gu

doi:10.1016/j.ejmech.2020.112076

Cited by 27 publications

(17 citation statements)

References 52 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A tumor-supporting role has also been suggested for Prostaglandin-Endoperoxide Synthase 2 (PTGS2) in HCC and colorectal cancer, which plays a critical role in the PI3K/AKT signaling pathway [ 35 , 36 ]. The identification of tumor-initiating activities of AKT1 inspired the application of an AKT1 inhibitor to stimulate autophagy-associated HCC cell death [ 37 ]. Similarly, the MAPK1 gene is also an oncogene leading to accelerated HCC cell proliferation, migration and invasion [ 38 ].…”

Section: Discussionmentioning

confidence: 99%

Molecular targets of Yangyin Fuzheng Jiedu Prescription in the treatment of hepatocellular carcinoma based on network pharmacology analysis

et al. 2020

View full text Add to dashboard Cite

Background Yangyin Fuzheng Jiedu Prescription (YFJP) is a traditional Chinese medicine (TCM) indicated for the treatment of hepatocellular carcinoma (HCC). Its potential targets and molecular mechanisms are not clear. Therefore, this study intends to explore the molecular mechanism of YFJP based on network pharmacology analysis and in vitro validation. Methods and results Through univariate and multivariate analyses and survival analysis in HCC patients with or without YFJP treatment we found that drinking alcohol, alfafeto protein ≥ 400 ng/l, baseline portal vein tumor thrombus and total bilirubin level ≥ 18.8 μM) were independent risk factors for poor prognosis, while red blood cell count ≥ 4 × 109/l and TCM treatment were independent protective factors. Besides, YFJP prolonged the cumulative survival of HCC patients. Using online pharmacological methods, we obtained 58 relevant compounds and molecular 53 targets. By using scratch test, Transwell assay, EdU assay, and TUNEL staining, we found that YFJP-containing serum repressed the migration, invasion and proliferation of HCC cells in vitro, and induced cell apoptosis. Moreover, YFJP diminished the gene expression of TP53, CCND1, p-EGFR, EGF, VEGFA, JUN, IL6, COX-2, AKT1, and MAPK1 in HCC cells, but elevated the expression of ESR1 and CASP3. Conclusions Taken together, results showed that YFJP attenuated HCC progression through mediating effects on HCC-related genes.

show abstract

Section: Discussionmentioning

confidence: 99%

Molecular targets of Yangyin Fuzheng Jiedu Prescription in the treatment of hepatocellular carcinoma based on network pharmacology analysis

et al. 2020

View full text Add to dashboard Cite

show abstract

“…All these proteins are involved in the PI3K-Akt signaling pathway; therefore, their inhibition or activation could cause disruption in processes such as apoptosis, cell differentiation and proliferation, angiogenesis, protein synthesis, DNA repair and metabolism [ 54 , 55 ]. Furthermore, the binding effect of 5-oxocoronaridine on AKT1 could have important biological activity by inhibiting the molecular function of apoptotic and coagulation proteins such as MCL1 and SERPINE1 respectively, which could lead to uncontrolled cellular proliferation and cardiac issues [ 56 ].…”

Section: Discussionmentioning

confidence: 99%

Molecular Human Targets of Bioactive Alkaloid-Type Compounds from Tabernaemontana cymose Jacq.

et al. 2021

View full text Add to dashboard Cite

Alkaloids are a group of secondary metabolites that have been widely studied for the discovery of new drugs due to their properties on the central nervous system and their anti-inflammatory, antioxidant and anti-cancer activities. Molecular docking was performed for 10 indole alkaloids identified in the ethanol extract of Tabernaemontana cymosa Jacq. with 951 human targets involved in different diseases. The results were analyzed through the KEGG and STRING databases, finding the most relevant physiological associations for alkaloids. The molecule 5-oxocoronaridine proved to be the most active molecule against human proteins (binding energy affinity average = −9.2 kcal/mol) and the analysis of the interactions between the affected proteins pointed to the PI3K/ Akt/mTOR signaling pathway as the main target. The above indicates that indole alkaloids from T. cymosa constitute a promising source for the search and development of new treatments against different types of cancer.

show abstract

“…Recently, there is evidence showing that novel AKT1 inhibitor could induce autophagy associated cell death. [53] And the dual suppression of the PI3K-AKT1-mTOR pathway by combination of rapamycin with Mono-Pt could better promote the generation of autophagy. [36] Thus, down-regulation of AKT1, PIK3R2, and PIK3R3 could mediate signaling pathways in autophagy and facilitate the autophagic cell death in Ir-Rhein-treated A549R cells.…”

Section: Rna Sequencing (Rna-seq) Transcriptome Analysismentioning

confidence: 99%

A New Strategy to Fight Metallodrug Resistance: Mitochondria‐Relevant Treatment through Mitophagy to Inhibit Metabolic Adaptations of Cancer Cells

Wang

et al. 2022

Angewandte Chemie

View full text Add to dashboard Cite

Metabolic adaptations can help cancer cells to escape from chemotherapeutics, mainly involving autophagy and ATP production. Herein, we report a new rhein‐based cyclometalated IrIII complex, Ir‐Rhein, that can accurately target mitochondria and effectively inhibit metabolic adaptations. The complex Ir‐Rhein induces severe mitochondrial damage and initiates mitophagy to reduce the number of mitochondria and subsequently inhibit both mitochondrial and glycolytic bioenergetics, which eventually leads to ATP starvation death. Moreover, Ir‐Rhein can overcome cisplatin resistance. Co‐incubation experiment, 3D tumor spheroids experiment and transcriptome analysis reveal that Ir‐Rhein shows promising antiproliferation performance for cisplatin‐resistant cancer cells with the regulation of platinum resistance‐related transporters. To our knowledge, this is a new strategy to overcome metallodrug resistance with a mitochondria‐relevant treatment.

show abstract

Discovery of novel akt1 inhibitor induces autophagy associated death in hepatocellular carcinoma cells

Cited by 27 publications

References 52 publications

Molecular targets of Yangyin Fuzheng Jiedu Prescription in the treatment of hepatocellular carcinoma based on network pharmacology analysis

Molecular targets of Yangyin Fuzheng Jiedu Prescription in the treatment of hepatocellular carcinoma based on network pharmacology analysis

Molecular Human Targets of Bioactive Alkaloid-Type Compounds from Tabernaemontana cymose Jacq.

A New Strategy to Fight Metallodrug Resistance: Mitochondria‐Relevant Treatment through Mitophagy to Inhibit Metabolic Adaptations of Cancer Cells

Contact Info

Product

Resources

About