scholarly journals Oncogene-induced reactive oxygen species fuel hyperproliferation and DNA damage response activation

2014 ◽  
Vol 21 (6) ◽  
pp. 998-1012 ◽  
Author(s):  
M Ogrunc ◽  
R Di Micco ◽  
M Liontos ◽  
L Bombardelli ◽  
M Mione ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Dna Damage ◽  
Dna Damage Response ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Damage Response ◽  
Response Activation

scholarly journals Phosphoinositide 3-Kinase (PI3K) Reactive Oxygen Species (ROS)-Activated Prodrug in Combination with Anthracycline Impairs PI3K Signaling, Increases DNA Damage Response and Reduces Breast Cancer Cell Growth

2021 ◽  
Vol 22 (4) ◽  
pp. 2088
Author(s):  
Rosalin Mishra ◽  
Long Yuan ◽  
Hima Patel ◽  
Aniruddha S. Karve ◽  
Haizhou Zhu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Reactive Oxygen Species ◽  
Dna Damage ◽  
Cell Growth ◽  
Cancer Cell ◽  
Dna Damage Response ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Cancer Cell Growth ◽  
Damage Response

RIDR-PI-103 is a novel reactive oxygen species (ROS)-induced drug release prodrug with a self-cyclizing moiety linked to a pan-PI3K inhibitor (PI-103). Under high ROS, PI-103 is released in a controlled manner to inhibit PI3K. The efficacy and bioavailability of RIDR-PI-103 in breast cancer remains unexplored. Cell viability of RIDR-PI-103 was assessed on breast cancer cells (MDA-MB-231, MDA-MB-361 and MDA-MB-453), non-tumorigenic MCF10A and fibroblasts. Matrigel colony formation, cell proliferation and migration assays examined the migratory properties of breast cancers upon treatment with RIDR-PI-103 and doxorubicin. Western blots determined the effect of doxorubicin ± RIDR-PI-103 on AKT activation and DNA damage response. Pharmacokinetic (PK) studies using C57BL/6J mice determined systemic exposure (plasma concentrations and overall area under the curve) and T1/2 of RIDR-PI-103. MDA-MB-453, MDA-MB-231 and MDA-MB-361 cells were sensitive to RIDR-PI-103 vs. MCF10A and normal fibroblast. Combination of doxorubicin and RIDR-PI-103 suppressed cancer cell growth and proliferation. Doxorubicin with RIDR-PI-103 inhibited p-AktS473, upregulated p-CHK1/2 and p-P53. PK studies showed that ~200 ng/mL (0.43 µM) RIDR-PI-103 is achievable in mice plasma with an initial dose of 20 mg/kg and a 10 h T1/2. (4) The prodrug RIDR-PI-103 could be a potential therapeutic for treatment of breast cancer patients.

scholarly journals Robust DNA Damage Response and Elevated Reactive Oxygen Species in TINF2-Mutated Dyskeratosis Congenita Cells

PLoS ONE ◽  
2016 ◽  
Vol 11 (2) ◽  
pp. e0148793 ◽  
Author(s):  
Larisa Pereboeva ◽  
Meredith Hubbard ◽  
Frederick D. Goldman ◽  
Erik R. Westin
Keyword(s):  
Reactive Oxygen Species ◽  
Dna Damage ◽  
Dna Damage Response ◽  
Reactive Oxygen ◽  
Dyskeratosis Congenita ◽  
Oxygen Species ◽  
Damage Response
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