scholarly journals Generation of reactive oxygen species is the primary mode of action and cause of survivin suppression by sepantronium bromide (YM155)

2021 ◽  
Author(s):  
Tasaduq Hussain Wani ◽  
Goutam Chowdhury ◽  
Anindita Chakrabarty
Keyword(s):  
Reactive Oxygen Species ◽  
Dna Damage ◽  
Mode Of Action ◽  
Reactive Oxygen ◽  
Cancer Drug ◽  
Oxygen Species ◽  
Secondary Effects ◽  
Primary Mode ◽  
Anti Cancer ◽  
Sepantronium Bromide

The anti-cancer drug YM155's primary mode of action is generation of reactive oxygen species, while survivin suppression and DNA damage are secondary effects.

scholarly journals Radiosensitizer Effect of β-Apopicropodophyllin against Colorectal Cancer via Induction of Reactive Oxygen Species and Apoptosis

2021 ◽  
Vol 22 (24) ◽  
pp. 13514
Author(s):  
Jin-Hee Kwon ◽  
Na-Gyeong Lee ◽  
A-Ram Kang ◽  
Jie-Young Song ◽  
Sang-Gu Hwang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Reactive Oxygen Species ◽  
Radiation Treatment ◽  
Combined Treatment ◽  
Reactive Oxygen ◽  
Cell Counting ◽  
Cancer Drug ◽  
Oxygen Species ◽  
In Vivo Animal Model ◽  
Anti Cancer

β-apopicropodophyllin (APP), a derivative of podophyllotoxin (PPT), has been identified as a potential anti-cancer drug. This study tested whether APP acts as an anti-cancer drug and can sensitize colorectal cancer (CRC) cells to radiation treatment. APP exerted an anti-cancer effect against the CRC cell lines HCT116, DLD-1, SW480, and COLO320DM, with IC50 values of 7.88 nM, 8.22 nM, 9.84 nM, and 7.757 nM, respectively, for the induction of DNA damage. Clonogenic and cell counting assays indicated that the combined treatment of APP and γ-ionizing radiation (IR) showed greater retardation of cell growth than either treatment alone, suggesting that APP sensitized CRC cells to IR. Annexin V–propidium iodide (PI) assays and immunoblot analysis showed that the combined treatment of APP and IR increased apoptosis in CRC cells compared with either APP or IR alone. Results obtained from the xenograft experiments also indicated that the combination of APP and IR enhanced apoptosis in the in vivo animal model. Apoptosis induction by the combined treatment of APP and IR resulted from reactive oxygen species (ROS). Inhibition of ROS by N-acetylcysteine (NAC) restored cell viability and decreased the induction of apoptosis by APP and IR in CRC cells. Taken together, these results indicate that a combined treatment of APP and IR might promote apoptosis by inducing ROS in CRC cells.

Aneugen Versus Clastogen Evaluation and Oxidative Stress-Related Mode-of-Action Assessment of Genotoxic Compounds Using the ToxTracker Reporter Assay

2020 ◽  
Vol 177 (1) ◽  
pp. 202-213
Author(s):  
Inger Brandsma ◽  
Nynke Moelijker ◽  
Remco Derr ◽  
Giel Hendriks
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Dna Damage ◽  
Mode Of Action ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Reporter Assay ◽  
Gfp Reporter ◽  
Genotoxic Compounds ◽  
And Oxidative Stress

Abstract Understanding the mode-of-action (MOA) of genotoxic compounds and differentiating between direct DNA interaction and indirect genotoxicity is crucial for their reliable safety assessment. ToxTracker is a stem cell-based reporter assay that detects activation of various cellular responses that are associated with genotoxicity and cancer. ToxTracker consists of 6 different GFP reporter cell lines that can detect the induction of DNA damage, oxidative stress, and protein damage in a single test. The assay can thereby provide insight into the MOA of compounds. Genotoxicity is detected in ToxTracker by activation of 2 independent GFP reporters. Activation of the Bscl2-GFP reporter is associated with induction of DNA adducts and subsequent inhibition of DNA replication and the Rtkn-GFP reporter is activated following the formation of DNA double-strand breaks. Here, we show that the differential activation of these 2 genotoxicity reporters could be used to further differentiate between a DNA reactive and clastogenic or a non-DNA-reactive aneugenic MOA of genotoxic compounds. For further classification of aneugenic and clastogenic compounds, the ToxTracker assay was extended with cell cycle analysis and aneuploidy assessment. The extension was validated using a selection of 16 (genotoxic) compounds with a well-established MOA. Furthermore, indirect genotoxicity related to the production of reactive oxygen species was investigated using the DNA damage and oxidative stress ToxTracker reporters in combination with different reactive oxygen species scavengers. With these new extensions, ToxTracker was able to accurately classify compounds as genotoxic or nongenotoxic and could discriminate between DNA-reactive compounds, aneugens, and indirect genotoxicity caused by oxidative stress.

scholarly journals Radiosensitizer Effect of β-Apopicropodophyllin Against Colorectal Cancer via Induction of Reactive Oxygen Species and Apoptosis

2021 ◽  
Author(s):  
Na-Gyeong Lee ◽  
Jin-Hee Kwon ◽  
A-Ram Kang ◽  
Jie-Young Song ◽  
Sang-Gu Hwang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Reactive Oxygen Species ◽  
Radiation Treatment ◽  
Combined Treatment ◽  
Reactive Oxygen ◽  
Cell Counting ◽  
Cancer Drug ◽  
Oxygen Species ◽  
In Vivo Animal Model ◽  
Anti Cancer

β-apopicropodophyllin (APP), a derivative of podophyllotoxin (PPT), has been identified as a potential anti-cancer drug. This study tested whether APP acts as an an-ti-cancer drug and can sensitize colorectal cancer (CRC) cells to radiation treatment. APP had an anti-cancer effect against the CRC cell lines HCT116, and DLD-1, SW480 and COLO320DM with IC50 values of 7.88 nM, and 8.22 nM, 9.84 nM and 7.757 nM, respec-tively induction of DNA damage. Colonogenic and cell counting assays indicated that the combined treatment of APP and γ-ionizing radiation (IR) showed greater retardation of cell growth than either alone, suggesting that APP sensitizes CRC cells to IR. Annexin V-propidium iodide (PI) assays and immunoblot analysis showed that the combined treatment of APP and IR increased apoptosis in CRC cells compared with either APP or IR alone. Results obtained from the xenograft experiments also indicated that the combination of APP and IR enhanced apoptosis in in vivo animal model. Apoptosis induction by the combined treatment of APP and IR resulted from reactive oxygen species (ROS). Inhibition of ROS by N-acetylcysteine (NAC) restored cell viability and decreased the induction of apoptosis by APP and IR in CRC cells. Taken together, these results indicate that a combined treatment of APP and IR might promote apoptosis by inducing ROS in CRC cells.

scholarly journals Targeted production of reactive oxygen species in mitochondria to overcome cancer drug resistance

2018 ◽  
Vol 9 (1) ◽  
Author(s):  
Hai Wang ◽  
Zan Gao ◽  
Xuanyou Liu ◽  
Pranay Agarwal ◽  
Shuting Zhao ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Drug Resistance ◽  
Reactive Oxygen ◽  
Cancer Drug ◽  
Oxygen Species ◽  
Cancer Drug Resistance
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