Artesunate induces autophagy dependent apoptosis through upregulating ROS and activating AMPK-mTOR-ULK1 axis in human bladder cancer cells

Zhou, Xinping; Chen, Yu; Wang, Feifan; Wu, Huitao; Zhang, Yan; Liu, Jiaxin; Cai, Yueshu; Huang, Song; He, Na; Hu, Zhenghui; Jin, Xiaodong

doi:10.1016/j.cbi.2020.109273

Cited by 53 publications

(30 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Notably, a positive association has also been identified between apoptosis and ROS production ( 60 , 61 ). Similar to previous reports ( 35 , 62 ), the results of the present study revealed that artesunate induced apoptosis in a ROS-dependent manner. In addition, the present study demonstrates that overexpression of MALAT1 or YAP reversed the antitumor effects of artesunate on ROS induction and apoptosis in C918 cells, indicating that MALAT1 or YAP may be potential drug targets for UM treatment.…”

Section: Discussionsupporting

confidence: 92%

“…In addition, the proliferation of hepatocellular carcinoma cells is suppressed by elevating the levels of apoptosis following CBX2 knockdown ( 34 ). Notably, artesunate exerts antitumor activity by enhancing apoptosis; Zhou et al ( 35 ) have reported that artesunate upregulates ROS levels and activates the AMP-activated protein kinase/mTOR/unc-51-like autophagy-activating kinase 1 axis in T24 cells, resulting in autophagy-dependent apoptosis of human bladder cancer. However, whether artesunate treatment enhances UM cell apoptosis and the potential underlying mechanisms of this effect are poorly understood.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Artesunate combined with verteporfin inhibits uveal melanoma by regulation of the MALAT1/yes‑associated protein signaling pathway

2021

View full text Add to dashboard Cite

Uveal melanoma (UM) is the most common ocular malignancy and has no effective clinical treatment. Therefore, novel drugs to suppress UM tumor progression are urgently required. The present study aimed to clarify the underlying mechanism of the inhibitory effects of artesunate on UM. By using plasmid transfection and detecting apoptotic level, the present study identified artesunate as a potential candidate for UM treatment. Compared with those in the vehicle (DMSO)-treated control cells, artesunate enhanced the apoptotic rate and increased lactate dehydrogenase release, reactive oxygen species and IL1b and IL18 levels in C918 cells. Overexpression of yes-associated protein (YAP) or metastasis-associated lung adenocarcinoma transcript 1 ( MALAT1 ) in C918 cells reversed the effects of artesunate and reduced the apoptotic rate compared with those observed in cells transfected with the negative control plasmid. Notably, verteporfin enhanced the effects of artesunate on C918 cells by increasing the apoptotic rate, indicating that combined therapy was more effective compared with treatment with artesunate alone. In conclusion, the results of the present study demonstrated that artesunate elevated the apoptotic rate and suppressed C918 cell viability by regulating the MALAT1 /YAP signaling pathway, and these effects were enhanced by supplementation with verteporfin. These results suggested that artesunate may exert an inhibitory effect on C918 cells and that the MALAT1 /YAP signaling may serve important role in mediating these effects, providing evidence of its potential for treating UM in the clinic.

show abstract

Section: Discussionsupporting

confidence: 92%

Section: Introductionmentioning

confidence: 99%

Artesunate combined with verteporfin inhibits uveal melanoma by regulation of the MALAT1/yes‑associated protein signaling pathway

2021

View full text Add to dashboard Cite

show abstract

“…The CTD database confirmed that succinic acid has various interactions with BCL2L1, including promoting product expression, promoting reaction activation, etc., and BCL2L1 is an expression product with a similar structure to BCL2. Moreover, artesunate [ 30 ] (dihydrocyanin-10-α- succinate) and 2,3-dimercaptosuccinic acid [ 31 ] (2,3-dimercaptosuccinic acid) can promote the expression and reaction of BCL2, and their molecular structures contain the succinic acid. This provides a reasonable explanation and support of the predicted result.…”

Section: Resultsmentioning

confidence: 99%

BioNet: a large-scale and heterogeneous biological network model for interaction prediction with graph convolution

Yang

Wang

et al. 2021

Briefings in Bioinformatics

View full text Add to dashboard Cite

Motivation Understanding chemical–gene interactions (CGIs) is crucial for screening drugs. Wet experiments are usually costly and laborious, which limits relevant studies to a small scale. On the contrary, computational studies enable efficient in-silico exploration. For the CGI prediction problem, a common method is to perform systematic analyses on a heterogeneous network involving various biomedical entities. Recently, graph neural networks become popular in the field of relation prediction. However, the inherent heterogeneous complexity of biological interaction networks and the massive amount of data pose enormous challenges. This paper aims to develop a data-driven model that is capable of learning latent information from the interaction network and making correct predictions. Results We developed BioNet, a deep biological networkmodel with a graph encoder–decoder architecture. The graph encoder utilizes graph convolution to learn latent information embedded in complex interactions among chemicals, genes, diseases and biological pathways. The learning process is featured by two consecutive steps. Then, embedded information learnt by the encoder is then employed to make multi-type interaction predictions between chemicals and genes with a tensor decomposition decoder based on the RESCAL algorithm. BioNet includes 79 325 entities as nodes, and 34 005 501 relations as edges. To train such a massive deep graph model, BioNet introduces a parallel training algorithm utilizing multiple Graphics Processing Unit (GPUs). The evaluation experiments indicated that BioNet exhibits outstanding prediction performance with a best area under Receiver Operating Characteristic (ROC) curve of 0.952, which significantly surpasses state-of-theart methods. For further validation, top predicted CGIs of cancer and COVID-19 by BioNet were verified by external curated data and published literature.

show abstract

“…Thus, ART has a dual anticancer effect on UCEC cells (37). ART also induces autophagy by upregulating ROS production and activating the AMP-activated protein kinase/mTOR/ULK1 pathway in human bladder cancer cells (9).…”

Section: Apoptosismentioning

confidence: 99%

“…However, accumulating evidence has shown that ART also displays anticancer properties, in addition to its antimalarial effect (8). For instance, ART has been reported to induce apoptosis and autophagy in human bladder cancer cells (9,10). Moreover, it can induce cell cycle arrest, reactive oxygen species (ROS) generation and ferroptosis in renal cell carcinoma (11).…”

Section: Introductionmentioning

confidence: 99%

Progress on the study of the anticancer effects of artesunate (Review)

et al. 2021

View full text Add to dashboard Cite

Artesunate (ART) is a derivative of artemisinin that is extracted from the wormwood plant Artemisia annua. ART is an antimalarial drug that has been shown to be safe and effective for clinical use. In addition to its antimalarial properties, ART has been attracting attention over recent years due to its reported inhibitory effects on cancer cell proliferation, invasion and migration. Therefore, ART has a wider range of potential clinical applications than first hypothesized. The aim of the present review was to summarize the latest research progress on the possible anticancer effects of ART, in order to lay a theoretical foundation for the further development of ART as a therapeutic option for cancer. Contents1. Introduction 2. Source and activity of ART 3. Anticarcinogenic mechanism of ART 4. Potential role of ART in human malignancies 5. Summary and perspectives

show abstract

Artesunate induces autophagy dependent apoptosis through upregulating ROS and activating AMPK-mTOR-ULK1 axis in human bladder cancer cells

Cited by 53 publications

References 37 publications

Artesunate combined with verteporfin inhibits uveal melanoma by regulation of the MALAT1/yes‑associated protein signaling pathway

Artesunate combined with verteporfin inhibits uveal melanoma by regulation of the MALAT1/yes‑associated protein signaling pathway

BioNet: a large-scale and heterogeneous biological network model for interaction prediction with graph convolution

Progress on the study of the anticancer effects of artesunate (Review)

Contact Info

Product

Resources

About