Prometryn induces apoptotic cell death through cell cycle arrest and oxidative DNA damage

Liu, Qiaoyun; Wang, Longsheng; Chen, Hanwen; Huang, Bo; Xu, Jiawei; Liu, Ying; Héroux, Paul; Zhu, Xinqiang; Xia, Dajing

doi:10.1039/c9tx00080a

Cited by 19 publications

(8 citation statements)

References 23 publications

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“…Additionally, DNA damage is closely associated with cell cycle alterations in mammalian cells [ 25 , 26 ]. Hence, we evaluated the effects of PM 2.5 on cell cycle alterations in HaCaT keratinocytes using flow cytometry.…”

Section: Resultsmentioning

confidence: 99%

Hesperidin Exhibits Protective Effects against PM2.5-Mediated Mitochondrial Damage, Cell Cycle Arrest, and Cellular Senescence in Human HaCaT Keratinocytes

et al. 2022

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Particulate matter 2.5 (PM2.5) exposure can trigger adverse health outcomes in the human skin, such as skin aging, wrinkles, pigment spots, and atopic dermatitis. PM2.5 is associated with mitochondrial damage and the generation of reactive oxygen species (ROS). Hesperidin is a bioflavonoid that exhibits antioxidant and anti-inflammatory properties. This study aimed to determine the mechanism underlying the protective effect of hesperidin on human HaCaT keratinocytes against PM2.5-induced mitochondrial damage, cell cycle arrest, and cellular senescence. Human HaCaT keratinocytes were pre-treated with hesperidin and then treated with PM2.5. Hesperidin attenuated PM2.5-induced mitochondrial and DNA damage, G0/G1 cell cycle arrest, and SA-βGal activity, the protein levels of cell cycle regulators, and matrix metalloproteinases (MMPs). Moreover, treatment with a specific c-Jun N-terminal kinase (JNK) inhibitor, SP600125, along with hesperidin markedly restored PM2.5-induced cell cycle arrest and cellular senescence. In addition, hesperidin significantly reduced the activation of MMPs, including MMP-1, MMP-2, and MMP-9, by inhibiting the activation of activator protein 1. In conclusion, hesperidin ameliorates PM2.5-induced mitochondrial damage, cell cycle arrest, and cellular senescence in human HaCaT keratinocytes via the ROS/JNK pathway.

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Section: Resultsmentioning

confidence: 99%

Hesperidin Exhibits Protective Effects against PM2.5-Mediated Mitochondrial Damage, Cell Cycle Arrest, and Cellular Senescence in Human HaCaT Keratinocytes

et al. 2022

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“…Triazine concentrations of up to 108 μ g/L have been reported in North America rivers [ 15 ]. In addition, all triazine herbicides and their degradation products are persistent in the environment, especially in air and water, and these pesticides can damage human cardiac and immune systems and endanger the health of humans, animals, and plants [ 16 ].…”

Section: Introductionmentioning

confidence: 99%

A Common Feature of Pesticides: Oxidative Stress—The Role of Oxidative Stress in Pesticide-Induced Toxicity

Sule

Condon

Gomes

2022

Oxidative Medicine and Cellular Longevity

185

102

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Pesticides are important chemicals or biological agents that deter or kill pests. The use of pesticides has continued to increase as it is still considered the most effective method to reduce pests and increase crop growth. However, pesticides have other consequences, including potential toxicity to humans and wildlife. Pesticides have been associated with increased risk of cardiovascular disease, cancer, and birth defects. Labels on pesticides also suggest limiting exposure to these hazardous chemicals. Based on experimental evidence, various types of pesticides all seem to have a common effect, the induction of oxidative stress in different cell types and animal models. Pesticide-induced oxidative stress is caused by both reactive oxygen species (ROS) and reactive nitrogen species (RNS), which are associated with several diseases including cancer, inflammation, and cardiovascular and neurodegenerative diseases. ROS and RNS can activate at least five independent signaling pathways including mitochondrial-induced apoptosis. Limited in vitro studies also suggest that exogenous antioxidants can reduce or prevent the deleterious effects of pesticides.

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“…This study showed that bufalin can significantly inhibit the proliferation and colony formation of U251 cells and cause structural loss of mitochondria and endoplasmic reticulum in these cells. The S-phase checkpoint is one of the important mechanisms of DNA damage repair, as this machinery senses whether the DNA of a cell is damaged and whether damaged DNA is repaired, thereby preventing damaged DNA from being replicated and passed down to daughter cells [ 21 – 23 ]. The results of our qRT-PCR experiments showed that the mRNA expression levels of Chk1, ATR, CDC25A and CDK2 in U251 cells treated with bufalin were significantly upregulated, and the ATR-Chk1-CDC25A-CDK2 pathway was activated to transmit DNA damage signals, which directly caused U251 cell cycle arrest in the S phase.…”

Section: Discussionmentioning

confidence: 99%

Bufalin induces mitochondrial dysfunction and promotes apoptosis of glioma cells by regulating Annexin A2 and DRP1 protein expression

et al. 2021

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Background Glioma is a common primary central nervous system tumour, and therapeutic drugs that can effectively improve the survival rate of patients in the clinic are lacking. Bufalin is effective in treating various tumours, but the mechanism by which it promotes the apoptosis of glioma cells is unclear. The aim of this study was to investigate the drug targets of bufalin in glioma cells and to clarify the apoptotic mechanism. Methods Cell viability and proliferation were evaluated by CCK-8 and colony formation assays. Then, the cell cycle and apoptosis, intracellular ion homeostasis, oxidative stress levels and mitochondrial damage were assessed after bufalin treatment. DARTS-PAGE technology was employed and LC–MS/MS was performed to explore the drug targets of bufalin in U251 cells. Molecular docking and western blotting were performed to identify potential targets. siRNA targeting Annexin A2 and the DRP1 protein inhibitor Mdivi-1 were used to confirm the targets of bufalin. Results Bufalin upregulated the expression of cytochrome C, cleaved caspase 3, p-Chk1 and p-p53 proteins to induce U251 cell apoptosis and cycle arrest in the S phase. Bufalin also induced oxidative stress in U251 cells, destroyed intracellular ion homeostasis, and caused mitochondrial damage. The expression of mitochondrial division-/fusion-related proteins in U251 cells was abnormal, the Annexin A2 and DRP1 proteins were translocated from the cytoplasm to mitochondria, and the MFN2 protein was released from mitochondria into the cytoplasm after bufalin treatment, disrupting the mitochondrial division/fusion balance in U251 cells. Conclusions Our research indicated that bufalin can cause Annexin A2 and DRP1 oligomerization on the surface of mitochondria and disrupt the mitochondrial division/fusion balance to induce U251 cell apoptosis. Graphic Abstract

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Prometryn induces apoptotic cell death through cell cycle arrest and oxidative DNA damage

Cited by 19 publications

References 23 publications

Hesperidin Exhibits Protective Effects against PM2.5-Mediated Mitochondrial Damage, Cell Cycle Arrest, and Cellular Senescence in Human HaCaT Keratinocytes

Hesperidin Exhibits Protective Effects against PM2.5-Mediated Mitochondrial Damage, Cell Cycle Arrest, and Cellular Senescence in Human HaCaT Keratinocytes

A Common Feature of Pesticides: Oxidative Stress—The Role of Oxidative Stress in Pesticide-Induced Toxicity

Bufalin induces mitochondrial dysfunction and promotes apoptosis of glioma cells by regulating Annexin A2 and DRP1 protein expression

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