DNA double‐strand breaks disrupted the spindle assembly in porcine oocytes

Wang, Hai Yang; Luo, Yan; Zhao, Minghui; Lin, Zili; Kwon, Jeongwoo; Cui, Xiang‐Shun; Kim, Nam‐Hyung

doi:10.1002/mrd.22602

Cited by 17 publications

(17 citation statements)

References 35 publications

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“…The maintenance of genomic stability after DNA toxicity mainly depends on the DNA damage repair system and the cell cycle checkpoint. DNA damage induces the arrest of the cell cycle at the G2/M phase to delay cell cycle progression, ensuring sufficient time to repair damaged DNA [59,60]. During DNA damage, ATM or ATR activates a variety of downstream pathways, including p53, which leads to cycle arrest or apoptosis [61][62][63].…”

Section: Discussionmentioning

confidence: 99%

A novel chalcone derivative has antitumor activity in melanoma by inducing DNA damage through the upregulation of ROS products

Li¹,

Long²,

Su³

et al. 2020

Cancer Cell Int

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Background: Melanoma is one of the most aggressive tumors with the remarkable characteristic of resistance to traditional chemotherapy and radiotherapy. Although targeted therapy and immunotherapy benefit advanced melanoma patient treatment, BRAFi (BRAF inhibitor) resistance and the lower response rates or severe side effects of immunotherapy have been observed, therefore, it is necessary to develop novel inhibitors for melanoma treatment. Methods:We detected the cell proliferation of lj-1-59 in different melanoma cells by CCK 8 and colony formation assay. To further explore the mechanisms of lj-1-59 in melanoma, we performed RNA sequencing to discover the pathway of differential gene enrichment. Western blot and Q-RT-PCR were confirmed to study the function of lj-1-59 in melanoma. Results:We found that lj-1-59 inhibits melanoma cell proliferation in vitro and in vivo, induces cell cycle arrest at the G2/M phase and promotes apoptosis in melanoma cell lines. Furthermore, RNA-Seq was performed to study alterations in gene expression profiles after treatment with lj-1-59 in melanoma cells, revealing that this compound regulates various pathways, such as DNA replication, P53, apoptosis and the cell cycle. Additionally, we validated the effect of lj-1-59 on key gene expression alterations by Q-RT-PCR. Our findings showed that lj-1-59 significantly increases ROS (reactive oxygen species) products, leading to DNA toxicity in melanoma cell lines. Moreover, lj-1-59 increases ROS levels in BRAFi -resistant melanoma cells, leading to DNA damage, which caused G2/M phase arrest and apoptosis. Conclusions:Taken together, we found that lj-1-59 treatment inhibits melanoma cell growth by inducing apoptosis and DNA damage through increased ROS levels, suggesting that this compound is a potential therapeutic drug for melanoma treatment.

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Section: Discussionmentioning

confidence: 99%

A novel chalcone derivative has antitumor activity in melanoma by inducing DNA damage through the upregulation of ROS products

Li¹,

Long²,

Su³

et al. 2020

Cancer Cell Int

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“…Western blotting was performed as described previously [30, 31], using the following antibody dilutions: anti-BCL-2, 1:500; anti-CDK1-pY15, 1:500; anti-cyclin B, 1:500; anti-β-actin, 1:2000.…”

Section: Methodsmentioning

confidence: 99%

Quercetin delays postovulatory aging of mouse oocytes by regulating SIRT expression and MPF activity

Wang

et al. 2017

Oncotarget

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If no fertilization occurs at an appropriate time after ovulation, oocyte quality deteriorates rapidly as a process called postovulatory aging. Because the postovulatory aging of oocytes has detrimental effects on embryo development and offspring, many efforts have been made to prevent oocyte aging. Here we showed that quercetin prevented the decline in oocyte quality during postovulatory aging of oocytes. Quercetin treatment reduced aging-induced morphological changes and reactive oxygen species accumulation. Moreover, quercetin attenuated the aging-associated abnormalities in spindle organization and mitochondrial distribution, preventing decrease of SIRT expression and histone methylation. Quercetin also ameliorated the decrease in maturation-promoting factor activity and the onset of apoptosis during postovulatory aging. Furthermore, quercetin treatment during postovulatory aging improves early embryo development. Our results demonstrate that quercetin relieves deterioration in oocyte quality and improves subsequent embryo development.

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“…Western blotting was performed as described previously [7]. A total of 300 porcine embryos per sample were placed in 1X SDS sample buffer and heated at 100°C for 5 min.…”

Section: Western Blot Analysismentioning

confidence: 99%

CDK2 Is Required for the DNA Damage Response During Porcine Early Embryonic Development

Wang

Kim

2016

Biology of Reproduction

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Cyclin-dependent kinase (CDK) 2 inhibition plays a central role in DNA damage-induced cell cycle arrest and DNA repair. However, whether CDK2 also influences early porcine embryo development is unknown. In this study, we examined whether CDK2 is involved in the regulation of oocyte meiosis and early embryonic development of porcine embryos. We found that disrupting CDK2 activity with RNAi or an inhibitor did not affect meiotic resumption or meiosis II arrest. However, CDK2 inhibitor-treated embryos showed delayed cleavage and ceased development before the blastocyst stage. Disrupting CDK2 activity is able to induce sustained DNA damage, as demonstrated by the formation of distinct gammaH2AX foci in nuclei of Day-3 and Day-5 embryos. Inhibiting CDK2 triggers a DNA damage checkpoint by activation of the ataxia telangiectasia mutated (ATM)-P53-P21 pathway. However, the mRNA expression of genes involved in nonhomologous end joining or homologous recombination pathways for double-strand break repair were reduced after administering CDK2 inhibitor to 5-day-old embryos. Furthermore, CDK2 inhibition caused apoptosis in Day-7 blastocysts. Thus, our results indicate that an ATM-P53-P21 DNA damage checkpoint is intact in the absence of CDK2; however, CDK2 is important for proper repair of the damaged DNA by either directly or indirectly influencing DNA repair-related gene expression.

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DNA double‐strand breaks disrupted the spindle assembly in porcine oocytes

Cited by 17 publications

References 35 publications

A novel chalcone derivative has antitumor activity in melanoma by inducing DNA damage through the upregulation of ROS products

A novel chalcone derivative has antitumor activity in melanoma by inducing DNA damage through the upregulation of ROS products

Quercetin delays postovulatory aging of mouse oocytes by regulating SIRT expression and MPF activity

CDK2 Is Required for the DNA Damage Response During Porcine Early Embryonic Development

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