Aa-Z2 triggers ROS-induced apoptosis of osteosarcoma by targeting PDK-1

Liu, Yixin; She, Wenyan; Li, Yang; Wang, Miao; Liu, Yin; Ning, Biao; Xu, Tianzi; Huang, Tianhe; Wei, Yongchang

doi:10.1186/s12967-022-03862-1

Cited by 6 publications

(4 citation statements)

References 51 publications

(44 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In research studies on the antitumor activity of the polyphenol agrimol B (Agr), it was found that Agr could increase the generation of ROS [ 41 ]. In addition, the organic arsenic compound Aa-Z2 induces ROS accumulation by targeting pyruvate dehydrogenase kinase 1 (PDK-1) to induce osteosarcoma apoptosis [ 42 ]. On the other hand, endogenous factors in the body can also lead to the excessive generation of ROS.…”

Section: Ros Levels In Cancer Cells and Cancer Developmentmentioning

confidence: 99%

Cancer Metabolism: The Role of ROS in DNA Damage and Induction of Apoptosis in Cancer Cells

Zhao

Xiong

et al. 2023

Metabolites

View full text Add to dashboard Cite

Cancer is a huge challenge for people worldwide. High reactive oxygen species (ROS) levels are a recognized hallmark of cancer and an important aspect of cancer treatment research. Abnormally elevated ROS levels are often attributable to alterations in cellular metabolic activities and increased oxidative stress, which affects both the development and maintenance of cancer. Moderately high levels of ROS are beneficial to maintain tumor cell genesis and development, while toxic levels of ROS have been shown to be an important force in destroying cancer cells. ROS has become an important anticancer target based on the proapoptotic effect of toxic levels of ROS. Therefore, this review summarizes the role of increased ROS in DNA damage and the apoptosis of cancer cells caused by changes in cancer cell metabolism, as well as various anticancer therapies targeting ROS generation, in order to provide references for cancer therapies based on ROS generation.

show abstract

Section: Ros Levels In Cancer Cells and Cancer Developmentmentioning

confidence: 99%

Cancer Metabolism: The Role of ROS in DNA Damage and Induction of Apoptosis in Cancer Cells

Zhao

Xiong

et al. 2023

Metabolites

View full text Add to dashboard Cite

show abstract

“…Apoptosis, as a programmed cell death mechanism, has gained significant attention in the pathogenesis of osteosarcoma [35]. Induction of apoptosis can effectively inhibit the growth and metastasis of osteosarcoma, making the induction of tumor cell apoptosis by TCM a potentially effective approach for treating osteosarcoma [36].…”

Section: Discussionmentioning

confidence: 99%

Network pharmacology and experimental validation to study the potential mechanism of Tongguanteng injection in regulating apoptosis in osteosarcoma

Wei,

Meng,

Xiang

et al. 2024

BMC Complement Med Ther

View full text Add to dashboard Cite

Objective The main objectives of this study were to identify the active components of Tongguanteng injection (TGT) and investigate the preclinical efficacy and mechanism of TGT on osteosarcoma using a combination of network pharmacology and experimental validation. Methods To identify the active constituents and targets of TGT against osteosarcoma using network pharmacology, we constructed a network consisting of an 'active ingredient-disease-target-pathway' and a protein–protein interaction (PPI) network. The target organ network was utilized to investigate the distribution of core targets in tissues. Afterwards, the core targets underwent Gene ontology (GO) functional enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. The binding energy between receptors and ligands was compared using molecular docking. In addition, SwissADME was employed to forecast the pharmacokinetic characteristics of the substances. Finally, real-time polymerase chain reaction (RT-PCR), cell proliferation assay, morphological analysis, apoptosis assay, mitochondrial membrane potential (MMP) detection, and Western blotting were utilized to confirm the potential mechanisms of TGT treatment in osteosarcoma cell lines 143B and SAOS2. Results A total of 54 chemical constituents of TGT and 71 targets associated with osteosarcoma were acquired. Through the molecular docking technology, Tenacigenin B, Marsdekoiside, Taraxasterol, Tenacissoside G, Tenacissoside L, and Tenacissoside J were identified as the primary active components of TGT among the various compounds. Analysis of target organs suggests that TGT may play an anti-osteosarcoma role through immune regulation. The GO and KEGG enrichment analysis revealed that TGT could trigger osteosarcoma cell apoptosis by inhibiting the HIF-1 signalling pathway and modulating PD-1 expression and the PD-1 checkpoint pathway in cancer. SwissADME database predicted that Tenacigenin B and Taraxasterol had the best drug-likeness. In vitro studies also demonstrated that TGT suppressed the activity and induced alterations in the morphology of osteosarcoma cells. It decreased MMP levels, triggered apoptosis by increasing Bax expression and Caspase-3 activity, and decreased Bcl-2 expression, thereby exerting an anti-osteosarcoma effect. In the meantime, RT-PCR tests demonstrated that TGT could control immune response against tumors and hinder the proliferation and spread of cancerous cells by impacting the levels of critical factors, including JUN, HSP90AA1, HDAC1, and CDK1. Conclusion The study accurately anticipated the active components, targets, and pathways of TGT in the management of osteosarcoma. The molecular mechanism of TGT-induced apoptosis in osteosarcoma cells was demonstrated by in vitro experiments. These results provide theoretical and technical support for TGT as a clinical adjuvant drug for osteosarcoma.

show abstract

“…Apoptosis, as a programmed cell death mechanism, has gained signi cant attention in the pathogenesis of osteosarcoma [31]. Induction of apoptosis can effectively inhibit the growth and metastasis of osteosarcoma, making the induction of tumor cell apoptosis by TCM a potentially effective approach for the treatment of osteosarcoma [32].…”

Section: Discussionmentioning

confidence: 99%

Network pharmacology and experimental validation to study the potential mechanism of Tongguanteng injection against osteosarcoma

Wei,

meng,

xiang

et al. 2023

Preprint

View full text Add to dashboard Cite

Objective The main objectives of this study were to identify the active components of TGT and investigate the preclinical efficacy and mechanism of TGT on osteosarcoma using a combination of network pharmacology and experimental validation. Methods To identify the active constituents and targets of TGT against osteosarcoma using network pharmacology, we constructed a network consisting of an 'active ingredient-disease-target-pathway' and a protein-protein interaction (PPI) network. The target organ network was utilized to investigate the distribution of core targets in tissues. Afterward, the core targets underwent Gene ontology (GO) functional enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. The comparison of binding energy between receptors and ligands was conducted using molecular docking. In addition, SwissADME was employed to forecast the pharmacokinetic characteristics of the substances. Finally, real-time polymerase chain reaction (RT-PCR), cell proliferation assay, morphological analysis, apoptosis assay, mitochondrial membrane potential (MMP) detection, and Western Blotting were utilized to confirm the potential mechanisms of TGT treatment in osteosarcoma cell lines 143B and SAOS2. Results A total of 54 chemical constituents of TGT and 71 targets associated with osteosarcoma were acquired. Through the molecular docking technology, Tenacigenin B, Marsdekoiside, Taraxasterol, Tenacissoside G, Tenacissoside L, and Tenacissoside J were identified as the primary active components of TGT among the various compounds. Analysis of target organs suggests that TGT may play an anti-osteosarcoma role through immune regulation. The analysis of GO and KEGG enrichment revealed that TGT can trigger osteosarcoma cell apoptosis by inhibiting the HIF-1 signaling pathway and modulating PD-1 expression and the PD-1 checkpoint pathway in cancer. SwissADME database predicted that Tenacigenin B and Taraxasterol had the best drug-likeness. In vitro studies also demonstrated that TGT suppressed the activity and induced alterations in the morphology of osteosarcoma cells. It decreased MMP levels, triggered apoptosis by increasing Bax expression and Caspase-3 activity, and decreased Bcl-2 expression, thereby exerting an anti-osteosarcoma effect. In the meantime, RT-PCR tests demonstrated that TGT can control immune response against tumors and hinder the proliferation and spread of cancerous cells through its impact on the levels of key factors including JUN, HSP90AA1, HDAC1, and CDK1. Conclusion The study accurately anticipated the active components, targets, and pathways of TGT in the management of osteosarcoma. The molecular mechanism of TGT induced apoptosis in osteosarcoma cells was demonstrated by in vitro experiments. These results provide theoretical and technical support for TGT as a clinical adjuvant drug for osteosarcoma.

show abstract

Aa-Z2 triggers ROS-induced apoptosis of osteosarcoma by targeting PDK-1

Cited by 6 publications

References 51 publications

Cancer Metabolism: The Role of ROS in DNA Damage and Induction of Apoptosis in Cancer Cells

Cancer Metabolism: The Role of ROS in DNA Damage and Induction of Apoptosis in Cancer Cells

Network pharmacology and experimental validation to study the potential mechanism of Tongguanteng injection in regulating apoptosis in osteosarcoma

Network pharmacology and experimental validation to study the potential mechanism of Tongguanteng injection against osteosarcoma

Contact Info

Product

Resources

About