Resveratrol induces DNA damage-mediated cancer cell senescence through the DLC1–DYRK1A–EGFR axis

Ma, Fengqiu; Ma, Yan; Liu, Keke; Gao, Junying; Li, Shasha; Sun, Xiaowen; Li, Guorong

doi:10.1039/d2fo01188c

Cited by 11 publications

(6 citation statements)

References 53 publications

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“…The imbalance of ROS induces adverse cancer outcomes by affecting signal transduction within the DDR [ 93 ] because the accumulation of ROS can be toxic to cells, and toxic levels of ROS have been shown to affect replication and transcription by inducing DNA strand breaks and base oxidation, which may lead to the accumulation of mutations in organisms and the transformation of tumors [ 94 ]. It was found that due to the increased expression of the tumor-suppressant gene deleted in liver cancer 1 (DLC1), ROS could further inhibit the DYRK1A–EGFR axis, triggering DNA damage, while the DNA double-strand break marker protein γH2AX was up-regulated and the DNA repair-related proteins p-BRCA1 and RAD51 were down-regulated, which contributed to tumor inhibition [ 95 ]. Irreversible DNA damage is a key factor in tumor cell apoptosis.…”

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

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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.

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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

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“…They become flattened and enlarged with large polypoid nuclei and lose their ability to divide [ 7 ]. These changes affect cytoskeleton integrity, cell proliferation, cell migration, and angiogenesis, leading to vascular dysfunction [ 30 , 31 ]. microRNA has been reported to be involved in regulating the pathological process of vascular disease progression, making it a potentially good candidate for stroke intervention.…”

Section: Discussionmentioning

confidence: 99%

miRNA-142-3p aggravates hydrogen peroxide-induced human umbilical vein endothelial cell premature senescence by targeting SIRT1

Tong,

Zhang,

Liu

et al. 2024

Bioscience Reports

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Vascular endothelial cell premature senescence plays an important part in stroke. Many microRNAs (miRNAs) are known to be involved in the pathological process of vascular endothelial cell premature senescence. This study aimed to investigate the mechanism of hydrogen peroxide (H2O2)-induced premature senescence in human umbilical vein endothelial cells (HUVECs) and effect of miR-142-3p on hydrogen peroxide (H2O2)-induced premature senescence. HUVECs were exposed to H2O2 to establish a model premature senescence in endothelial cells. CCK-8 assay was performed to detect cell viability. Senescence-associated β-galactosidase staining assay and senescence-related proteins p16 and p21 were used to detect changes in the degree of cell senescence. RT-qPCR and Western blot were conducted to measure mRNA and protein levels, respectively. The scratch wound-healing assay, transwell assay, and EdU assay were performed to evaluate the ability of migration and proliferation, respectively. miRNA-142-3p and silencing information regulator 2 related enzyme 1 (SIRT1) binding was verified using Targetscan software and a dual-luciferase assay. We found that miRNA-142-3p is abnormally upregulated in HUVECs treated with H2O2. Functionally, miRNA-142-3p inhibition may mitigate the degree of HUVEC senescence and improve HUVEC migration and proliferation. Mechanistically, SIRT1 was validated to be targeted by miRNA-142-3p in HUVECs. Moreover, SIRT1 inhibition reversed the effects of miRNA-142-3p inhibition on senescent HUVECs exposed to H2O2. To our knowledge, this is the first study to show that miRNA-142-3p ameliorates H2O2-induced HUVECs premature senescence by targeting SIRT1 and may shed light on the role of the miR-142-3p/SIRT1 axis in stroke treatment.

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“…46 induced DNA damage mediated cancer cell senescence by upregulating the γH2AX and downregulating the DNA repair proteins such as p‐BRCA (breast cancer gene 1) and RAD51 (RADiation sensitive protein 51 recombinase). Also, 46 effectively inhibited the volume of the transplanted tumors in a chicken embryo allantoic membrane xenograft tumor model (; Ma et al, 2023).…”

Section: Novel Drug Candidates Obtained From Natural Sources With Egf...mentioning

confidence: 99%

Targeting epidermal growth factor receptor and its downstream signaling pathways by natural products: A mechanistic insight

Damare,

Engle,

Kumar

2024

Phytotherapy Research

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The epidermal growth factor receptor (EGFR) is a transmembrane receptor tyrosine kinase (RTK) that maintains normal tissues and cell signaling pathways. EGFR is overactivated and overexpressed in many malignancies, including breast, lung, pancreatic, and kidney. Further, the EGFR gene mutations and protein overexpression activate downstream signaling pathways in cancerous cells, stimulating the growth, survival, resistance to apoptosis, and progression of tumors. Anti‐EGFR therapy is the potential approach for treating malignancies and has demonstrated clinical success in treating specific cancers. The recent report suggests most of the clinically used EGFR tyrosine kinase inhibitors developed resistance to the cancer cells. This perspective provides a brief overview of EGFR and its implications in cancer. We have summarized natural products‐derived anticancer compounds with the mechanistic basis of tumor inhibition via the EGFR pathway. We propose that developing natural lead molecules into new anticancer agents has a bright future after clinical investigation.

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Resveratrol induces DNA damage-mediated cancer cell senescence through the DLC1–DYRK1A–EGFR axis

Abstract: Inducing cell senescence is widely regarded as a potent tumor suppression mechanism. Resveratrol has attracted increasing attention for its capacity to prevent and suppress cancer. However, the mechanism of resveratrol...

Cited by 11 publications

References 53 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

miRNA-142-3p aggravates hydrogen peroxide-induced human umbilical vein endothelial cell premature senescence by targeting SIRT1

Targeting epidermal growth factor receptor and its downstream signaling pathways by natural products: A mechanistic insight

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