A novel DNA repair inhibitor, diallyl disulfide (DADS), impairs DNA resection during DNA double-strand break repair by reducing Sae2 and Exo1 levels

Kuo, Chun-Chi; Leu, Yann‐Lii; Wang, Tong Hong; Tseng, Wei-Che; Feng, Chun-Hao; Wang, Shu-Huei; Chen, Chin-Chuan

doi:10.1016/j.dnarep.2019.102690

Cited by 12 publications

(9 citation statements)

References 55 publications

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“…Although often highly expressed in cancer cells, its role in neuroblastoma remains unstudied. Diallyl disulphide (DADS), a compound found in garlic, has shown therapeutic potential in reducing EXO1 levels and in turn inhibiting DNA resection and repair, though its exact mechanism remains unknown [35]. RNASEH2A is also novel for neuroblastoma, however putative HIV RNASEH2 drugs (RHI001 and RHI002) have been shown to inhibit human RNASEH2 and decrease cell numbers of the neuroblastoma cell line, SK-N-SH [36].…”

Section: Rbps Involved In Replication Stress and Telomere Maintenancementioning

confidence: 99%

Identification of RNA-Binding Proteins as Targetable Putative Oncogenes in Neuroblastoma

Bell

Hagemann

Holien

et al. 2020

IJMS

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Neuroblastoma is a common childhood cancer with almost a third of those affected still dying, thus new therapeutic strategies need to be explored. Current experimental therapies focus mostly on inhibiting oncogenic transcription factor signalling. Although LIN28B, DICER and other RNA-binding proteins (RBPs) have reported roles in neuroblastoma development and patient outcome, the role of RBPs in neuroblastoma is relatively unstudied. In order to elucidate novel RBPs involved in MYCN-amplified and other high-risk neuroblastoma subtypes, we performed differential mRNA expression analysis of RBPs in a large primary tumour cohort (n = 498). Additionally, we found via Kaplan–Meier scanning analysis that 685 of the 1483 tested RBPs have prognostic value in neuroblastoma. For the top putative oncogenic candidates, we analysed their expression in neuroblastoma cell lines, as well as summarised their characteristics and existence of chemical inhibitors. Moreover, to help explain their association with neuroblastoma subtypes, we reviewed candidate RBPs’ potential as biomarkers, and their mechanistic roles in neuronal and cancer contexts. We found several highly significant RBPs including RPL22L1, RNASEH2A, PTRH2, MRPL11 and AFF2, which remain uncharacterised in neuroblastoma. Although not all RBPs appear suitable for drug design, or carry prognostic significance, we show that several RBPs have strong rationale for inhibition and mechanistic studies, representing an alternative, but nonetheless promising therapeutic strategy in neuroblastoma treatment.

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Section: Rbps Involved In Replication Stress and Telomere Maintenancementioning

confidence: 99%

Identification of RNA-Binding Proteins as Targetable Putative Oncogenes in Neuroblastoma

Bell

Hagemann

Holien

et al. 2020

IJMS

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“…To identify compounds that can inhibit DDR, the previously established SSA yeast-cell analysis system was adopted for screening ( Figure 1 a) [ 41 ]. The natural compounds used for screening were kindly provided from Professor Yann-Lii Leu.…”

Section: Resultsmentioning

confidence: 99%

“…Several natural compounds and their derivatives, such as paclitaxel, curcumin, and camptothecin, have demonstrated good results in clinical trials for the treatment of melanoma and cancers of the breast, lung, colon and rectum, etc., leading to a considerable improvement in the patient survival [ 36 , 37 ]. Furthermore, multiple Chinese herbal extracts, including sulforaphane, resveratrol, and diallyl disulfide, inhibit DDR, making them suitable for use as chemotherapy or radiotherapy adjuvants in cancer treatment [ 38 , 39 , 40 , 41 ].…”

Section: Introductionmentioning

confidence: 99%

Hydroxygenkwanin Increases the Sensitivity of Liver Cancer Cells to Chemotherapy by Inhibiting DNA Damage Response in Mouse Xenograft Models

Chen

Cheng

Shieh

et al. 2021

IJMS

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Molecules involved in DNA damage response (DDR) are often overexpressed in cancer cells, resulting in poor responses to chemotherapy and radiotherapy. Although treatment efficacy can be improved with the concomitant use of DNA repair inhibitors, the accompanying side effects can compromise the quality of life of patients. Therefore, in this study, we identified a natural compound that could inhibit DDR, using the single-strand annealing yeast-cell analysis system, and explored its mechanisms of action and potential as a chemotherapy adjuvant in hepatocellular carcinoma (HCC) cell lines using comet assay, flow cytometry, Western blotting, immunofluorescence staining, and functional analyses. We developed a mouse model to verify the in vitro findings. We found that hydroxygenkwanin (HGK) inhibited the expression of RAD51 and progression of homologous recombination, thereby suppressing the ability of the HCC cell lines to repair DNA damage and enhancing their sensitivity to doxorubicin. HGK inhibited the phosphorylation of DNA damage checkpoint proteins, leading to apoptosis in the HCC cell lines. In the mouse xenograft model, HGK enhanced the sensitivity of liver cancer cells to doxorubicin without any physiological toxicity. Thus, HGK can inhibit DDR in liver cancer cells and mouse models, making it suitable for use as a chemotherapy adjuvant.

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“…To maintain genome stability, organisms have evolved a complex network of DNA damage response (DDR) mechanisms, including DNA repair, DNA damage checkpoint mechanisms and programmed cell death. Double‑strand break sensor (DSB) induces activation of the DNA damage checkpoint, resulting in cell cycle arrest to allow enough time for DSB repair and prevent mitosis in the presence of a broken chromosome [30] . DDR is a kinase‑based signal transduction pathway that involves multiple DSB sensor proteins such as DNA repair proteins, transducer proteins such as ATM and ATR, mediator proteins such as 53BP1 and BRCA1, and effectors such as Chk1 and Chk2, which protect and maintain genome stability [ 31 , 32 ].…”

Section: Discussionmentioning

confidence: 99%

Synergic radiosensitization of sinomenine hydrochloride and radioiodine on human papillary thyroid carcinoma cells

Zhao

Zhang

Liu

et al. 2021

Translational Oncology

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Highlights This is the first time to study and find out that sinomenine hydrochloride and iodine-131 synergic enhance the apoptosis and regulate DNA repair and cell cycle checkpoint on papillary thyroid carcinoma cells. This is the first time to study and find out that sinomenine hydrochloride increased the radiosensitivity of papillary thyroid carcinoma cells and normal thyroid cells. This is the first time to study and find out that sinomenine hydrochloride could be a potential therapeutic radiosensitizer in papillary thyroid carcinoma radiotherapy after total thyroidectomy .

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A novel DNA repair inhibitor, diallyl disulfide (DADS), impairs DNA resection during DNA double-strand break repair by reducing Sae2 and Exo1 levels

Cited by 12 publications

References 55 publications

Identification of RNA-Binding Proteins as Targetable Putative Oncogenes in Neuroblastoma

Identification of RNA-Binding Proteins as Targetable Putative Oncogenes in Neuroblastoma

Hydroxygenkwanin Increases the Sensitivity of Liver Cancer Cells to Chemotherapy by Inhibiting DNA Damage Response in Mouse Xenograft Models

Synergic radiosensitization of sinomenine hydrochloride and radioiodine on human papillary thyroid carcinoma cells

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