Targeting Werner syndrome protein sensitizes U-2 OS osteosarcoma cells to selenium-induced DNA damage response and necrotic death

Cheng, Wen‐Hsing; Wu, Ryan T.Y.; Wu, Min; Rocourt, Caroline; Carrillo, José A.; Song, Jiuzhou; Bohr, Christina T.; Tzeng, Tiffany J.

doi:10.1016/j.bbrc.2012.02.104

Cited by 10 publications

(15 citation statements)

References 39 publications

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“…Accumulating evidence indicates that above a basal level, ROS have detrimental effects on the cell and can lead to various cellular events, including the regulation of cell death [34][35][36]. The accumulation of increased ROS is associated with DNA damage, and evidence suggests that this type of stress-induced DNA damage can cause cell death via necrosis [21,[37][38][39]. Overproduction of ROS can lead to the accumulation of DNA strand breaks (DSBs), DNA intra-strand adducts, and DNA-protein crosslinks [40].…”

Section: Introductionmentioning

confidence: 99%

Lycorine induces programmed necrosis in the multiple myeloma cell line ARH-77

et al. 2014

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Lycorine, a natural alkaloid, has been widely reported to possess potential efficacy against cancer. However, the anti-multiple myeloma mechanism of lycorine is not fully understood. In this study, the results demonstrated that lycorine is effective against multiple myeloma cell line ARH-77 via inducing programmed necrosis. The mechanisms of lycorine on the multiple myeloma cell line ARH-77 are associated with G1 phase cell cycle arrest, mitochondrial dysfunction, reactive oxygen species (ROS) generation, ATP depletion, and DNA damage. Our results elucidate the new mechanism of lycorine against multiple myeloma.

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Section: Introductionmentioning

confidence: 99%

Lycorine induces programmed necrosis in the multiple myeloma cell line ARH-77

et al. 2014

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“…We have previously shown that MSeA treatment (LD 50 , 4 µmol/L) kills HCT116 colorectal, PC-3 prostate and U-2 OS osteosarcoma cells in association with reactive oxygen species (ROS), ATM and DNA-PK cs [12], [13]. Because ROS are also implicated in Notch3 signaling pathway [42], [43], we tested the hypothesis that MSeA could repress the desensitization of OVCA429/NICD3 ovarian cancer cells to carboplatin.…”

Section: Resultsmentioning

confidence: 99%

“…Flow cytometric analyses of cell cycle were performed as described previously [12]. Cells were analyzed by a FACScalibur cytometer with CELLQuest program (Becton Dickinson, San Jose, CA).…”

Section: Methodsmentioning

confidence: 99%

“…MSeA is metabolized to methylselenol, eventually resulting in the formation of selenium dioxide, superoxide anion, and hydrogen peroxide [10], [11]. Furthermore, MSeA can activate ataxia-telangiectasia mutated (ATM) and the catalytic subunit of DNA-dependent protein kinase (DNA-PK cs ), two critical DNA damage response kinases, in cancer cells [12]–[14].…”

Section: Introductionmentioning

confidence: 99%

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Methylseleninic Acid Sensitizes Notch3-Activated OVCA429 Ovarian Cancer Cells to Carboplatin

Tzeng

Cao

et al. 2014

PLoS ONE

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Ovarian cancer, the deadliest of gynecologic cancers, is usually not diagnosed until advanced stages. Although carboplatin has been popular for treating ovarian cancer for decades, patients eventually develop resistance to this platinum-containing drug. Expression of neurogenic locus notch homolog 3 (Notch3) is associated with chemoresistance and poor overall survival in ovarian cancer patients. Overexpression of NICD3 (the constitutively active form of Notch3) in OVCA429 ovarian cancer cells (OVCA429/NICD3) renders them resistance to carboplatin treatment compared to OVCA429/pCEG cells expressing an empty vector. We have previously shown that methylseleninic acid (MSeA) induces oxidative stress and activates ataxia-telangiectasia mutated and DNA-dependent protein kinase in cancer cells. Here we tested the hypothesis that MSeA and carboplatin exerted a synthetic lethal effect on OVCA429/NICD3 cells. Co-treatment with MSeA synergistically sensitized OVCA429/NICD3 but not OVCA429/pCEG cells to the killing by carboplatin. This synergism was associated with a cell cycle exit at the G2/M phase and the induction of NICD3 target gene HES1. Treatment of N-acetyl cysteine or inhibitors of the above two kinases did not directly impact on the synergism in OVCA429/NICD3 cells. Taken together, these results suggest that the efficacy of carboplatin in the treatment of high grade ovarian carcinoma can be enhanced by a combinational therapy with MSeA.

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“…103 RecQ-like helicases play key roles in DNA replication, recombination, and repair; stabilize the replication fork; and are needed for telomere stability. 52 As evidence that targeting RecQ-like helicases might aid chemotherapy, cells exposed to small hairpin RNA (shRNA) targeting WRN are more sensitive to methylselenic acid, 104 and cells with mutated WRN respond more slowly to DNA damage from UV light or chemotherapeutic agents, such as the topoisomerase inhibitor camptothecin. 105 RecQ5 also aids in the recovery of stalled replication forks after camptothecin treatment.…”

Section: Introduction To Helicase Structure and Functionmentioning

confidence: 99%

Discovering New Medicines Targeting Helicases: Challenges and Recent Progress

et al. 2013

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Helicases are ubiquitous motor proteins that separate and/or rearrange nucleic acid duplexes in reactions fueled by adenosine triphosphate (ATP) hydrolysis. Helicases encoded by bacteria, viruses, and human cells are widely studied targets for new antiviral, antibiotic, and anticancer drugs. This review summarizes the biochemistry of frequently targeted helicases. These proteins include viral enzymes from herpes simplex virus, papillomaviruses, polyomaviruses, coronaviruses, the hepatitis C virus, and various flaviviruses. Bacterial targets examined include DnaB-like and RecBCD-like helicases. The human DEAD-box protein DDX3 is the cellular antiviral target discussed, and cellular anticancer drug targets discussed are the human RecQ-like helicases and eIF4A. We also review assays used for helicase inhibitor discovery and the most promising and common helicase inhibitor chemotypes, such as nucleotide analogues, polyphenyls, metal ion chelators, flavones, polycyclic aromatic polymers, coumarins, and various DNA binding pharmacophores. Also discussed are common complications encountered while searching for potent helicase inhibitors and possible solutions for these problems.

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Targeting Werner syndrome protein sensitizes U-2 OS osteosarcoma cells to selenium-induced DNA damage response and necrotic death

Cited by 10 publications

References 39 publications

Lycorine induces programmed necrosis in the multiple myeloma cell line ARH-77

Lycorine induces programmed necrosis in the multiple myeloma cell line ARH-77

Methylseleninic Acid Sensitizes Notch3-Activated OVCA429 Ovarian Cancer Cells to Carboplatin

Discovering New Medicines Targeting Helicases: Challenges and Recent Progress

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