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• W4281680517 endingPage "3567" @default.
• W4281680517 startingPage "3567" @default.
• W4281680517 abstract "Recently, we identified secalonic acid F (SA), 5-epi-nakijiquinone Q (NQ) and 5-epi-ilimaquinone (IQ) as natural compounds (NC) affecting mechanisms of the DNA damage response (DDR). Here, we further characterized their effects on DDR, DNA repair and cytotoxicity if used in mono- and co-treatment with conventional anticancer therapeutics (cAT) (cisplatin (Cis), doxorubicin (Doxo)) in vitro. All three NC influence the phosphorylation level of selected DDR-related factors (i.e., pCHK1, pKAP1, pP53, pRPA32) in mono- and/or co-treatment. Both SA and NQ attenuate the Cis- and Doxo-induced G2/M-phase arrest and effectively stimulate caspase-mediated apoptosis. Notably, SA impacts DNA repair as reflected by enhanced steady-state levels of Cis-(1,2-GpG)-DNA adducts and Doxo-induced DNA double-strand breaks (DSB). Moreover, SA decreased the mRNA and protein expression of the homologous recombination (HR)-related DSB repair factors RAD51 and BRCA1. Both SA and NQ promote Cis- and Doxo-induced cytotoxicity in an additive to synergistic manner (CI ≤ 1.0). Summarizing, we conclude that SA promotes cAT-driven caspase-dependent cell death by interfering with DSB repair and DDR-related checkpoint control mechanisms. Hence, SA is considered as the most promising lead compound to evaluate its therapeutic window in forthcoming pre-clinical in vivo studies." @default.
• W4281680517 created "2022-06-13" @default.
• W4281680517 creator A5018660823 @default.
• W4281680517 creator A5040178005 @default.
• W4281680517 creator A5054098212 @default.
• W4281680517 creator A5077464087 @default.
• W4281680517 date "2022-06-01" @default.
• W4281680517 modified "2023-09-30" @default.
• W4281680517 title "Targeting Mechanisms of the DNA Damage Response (DDR) and DNA Repair by Natural Compounds to Improve cAT-Triggered Tumor Cell Death" @default.
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• W4281680517 doi "https://doi.org/10.3390/molecules27113567" @default.
• W4281680517 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/35684504" @default.
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