Nonhomologous end joining and homologous recombination involved in luteolin-induced DNA damage in DT40 cells

Xiang, Cuifang; Wu, Xiaohua; Zhao, Zilu; Feng, Xiaoyu; Bai, Xin; Liu, Xin; Zhao, Jingxia; Takeda, Shunichi; Qing, Yong

doi:10.1016/j.tiv.2020.104825

Cited by 6 publications

(5 citation statements)

References 46 publications

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“…The most sensitive mutants were NHEJ (KU70, LIGIV, and DNA-PKCS)-deficient cells. These results are consistent with previous studies showing that NHEJ-deficient cells derived from DT40 cells are extremely sensitive to Topo2 inhibitors. − HR-deficient cells, especially FANC/BRCA-deficient cells, were also highly sensitive to DOX. The susceptibility of HR-deficient DT40 cells in this study is in contrast to results from most of the previously reports using DT40 mutants demonstrating that HR-deficient isogenic cells (except BRCA2 mutants) were similarly susceptible to DT40 parental cells. , The likely reason for the discrepancy between the present results and previous reports is the presence or absence of 50 μM mercaptoethanol in the cell culture.…”

Section: Resultssupporting

confidence: 92%

Potential Doxorubicin-Mediated Dual-Targeting Chemotherapy in FANC/BRCA-Deficient Tumors via Modulation of Cellular Formaldehyde Concentration

Nakamura

2020

Chem. Res. Toxicol.

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Doxorubicin (DOX) is a widely used classical broad-spectrum anticancer drug. The major mechanism of DOX-mediated anticancer activity at clinically relevant concentrations is believed to be via DNA double-strand breaks due to topoisomerase IIα. However, other mechanisms by which DOX causes cytotoxicity have been proposed, including formaldehyde-dependent virtual interstrand cross-linking (ICL) formation. In this study, a method was established whereby cytotoxicity caused by virtual ICL derived from DOX is turned on and off using a cell culture system. Using this strategy, DOX-mediated cytotoxicity in Fanconi anemia group gene (FANC)/breast cancer susceptibility gene (BRCA)-deficient cells increased up to 70-fold compared to that in cells proficient in DNA repair pathways by increasing intracellular formaldehyde (FA) concentration. This approach also demonstrated that cytotoxicity introduced by DOX-mediated FA-dependent virtual ICL is completely independent of the toxicity induced by topoisomerase II inhibition at the cellular level. The potential of dual-targeting by DOX treatment was verified using an acid-specific FA donor. Overall, anticancer therapy targeting tumors deficient in the FANC/BRCA pathway may be possible by minimizing DOX-induced toxicity in normal cells.

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Section: Resultssupporting

confidence: 92%

Potential Doxorubicin-Mediated Dual-Targeting Chemotherapy in FANC/BRCA-Deficient Tumors via Modulation of Cellular Formaldehyde Concentration

Nakamura

2020

Chem. Res. Toxicol.

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“…Inhibited the EMT [376,381,384]. Inflicted double-stranded DNA breaks and prevented nonhomologous end joining [385]. Induced apoptosis [374,375,382,[386][387][388].…”

Section: Luteolinmentioning

confidence: 99%

“…HIF-1α/VEGF signaling-mediated epithelial to mesenchymal transition and angiogenesis was implicated in the anti-metastatic effects demonstrated by luteolin [379]. Luteolin caused double-strand DNA breaks and prevented nonhomologous end joining (NHEJ) and homologous recombination (HR) in a bursal lymphoma model, and additionally caused G2/M phase cell cycle arrest in BRCA-deficient cells and inhibited Poly [ADP-ribose] polymerase 1 (PARP1) [362,385].…”

Section: Luteolinmentioning

confidence: 99%

Anti-Cancer Potential of Cannabinoids, Terpenes, and Flavonoids Present in Cannabis

Tomko

Whynot

Ellis

et al. 2020

Cancers

149

139

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In recent years, and even more since its legalization in several jurisdictions, cannabis and the endocannabinoid system have received an increasing amount of interest related to their potential exploitation in clinical settings. Cannabinoids have been suggested and shown to be effective in the treatment of various conditions. In cancer, the endocannabinoid system is altered in numerous types of tumours and can relate to cancer prognosis and disease outcome. Additionally, cannabinoids display anticancer effects in several models by suppressing the proliferation, migration and/or invasion of cancer cells, as well as tumour angiogenesis. However, the therapeutic use of cannabinoids is currently limited to the treatment of symptoms and pain associated with chemotherapy, while their potential use as cytotoxic drugs in chemotherapy still requires validation in patients. Along with cannabinoids, cannabis contains several other compounds that have also been shown to exert anti-tumorigenic actions. The potential anti-cancer effects of cannabinoids, terpenes and flavonoids, present in cannabis, are explored in this literature review.

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“…Luteolin can remarkably induce DNA double-strand breaks (DSBs) in DT40 cells and induce sensitivity and defects in DSB repair in Ku70 cells. Furthermore, it improves the formation of Top2cc in Ku70 cells [ 346 ]. Luteolin and its derivative apigenin significantly inhibit lung cancer cell growth and downregulate the IFN-γ-induced PD-L1 expression by suppressing the phosphorylation of STAT3 [ 347 ].…”

Section: Plant-derived Natural Products With Potential Anticancer Eff...mentioning

confidence: 99%

Plants as a Source of Anticancer Agents: From Bench to Bedside

et al. 2022

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Cancer is the second leading cause of death after cardiovascular diseases. Conventional anticancer therapies are associated with lack of selectivity and serious side effects. Cancer hallmarks are biological capabilities acquired by cancer cells during neoplastic transformation. Targeting multiple cancer hallmarks is a promising strategy to treat cancer. The diversity in chemical structure and the relatively low toxicity make plant-derived natural products a promising source for the development of new and more effective anticancer therapies that have the capacity to target multiple hallmarks in cancer. In this review, we discussed the anticancer activities of ten natural products extracted from plants. The majority of these products inhibit cancer by targeting multiple cancer hallmarks, and many of these chemicals have reached clinical applications. Studies discussed in this review provide a solid ground for researchers and physicians to design more effective combination anticancer therapies using plant-derived natural products.

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Nonhomologous end joining and homologous recombination involved in luteolin-induced DNA damage in DT40 cells

Cited by 6 publications

References 46 publications

Potential Doxorubicin-Mediated Dual-Targeting Chemotherapy in FANC/BRCA-Deficient Tumors via Modulation of Cellular Formaldehyde Concentration

Potential Doxorubicin-Mediated Dual-Targeting Chemotherapy in FANC/BRCA-Deficient Tumors via Modulation of Cellular Formaldehyde Concentration

Anti-Cancer Potential of Cannabinoids, Terpenes, and Flavonoids Present in Cannabis

Plants as a Source of Anticancer Agents: From Bench to Bedside

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