Contribution of reactive oxygen species to ovarian cancer cell growth arrest and killing by the anti-malarial drug artesunate

2016 ◽  
Vol 56 (1) ◽  
pp. 75-93 ◽  
Author(s):  
Anna L. Greenshields ◽  
Trevor G. Shepherd ◽  
David W. Hoskin
2013 ◽  
Vol 58 (9) ◽  
pp. 2518-2527 ◽  
Author(s):  
Wen-Bo Chen ◽  
Feng-Ting Huang ◽  
Yan-Yan Zhuang ◽  
Jian Tang ◽  
Xiao-Hong Zhuang ◽  
...  

2021 ◽  
Vol 22 (4) ◽  
pp. 2088
Author(s):  
Rosalin Mishra ◽  
Long Yuan ◽  
Hima Patel ◽  
Aniruddha S. Karve ◽  
Haizhou Zhu ◽  
...  

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.


Oncotarget ◽  
2015 ◽  
Vol 6 (28) ◽  
pp. 25917-25931 ◽  
Author(s):  
Liping Wang ◽  
Zhufang Tian ◽  
Qi Yang ◽  
Heng Li ◽  
Haixia Guan ◽  
...  

Cancers ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 2061
Author(s):  
Cecilia Pozzi ◽  
Matteo Santucci ◽  
Gaetano Marverti ◽  
Domenico D’Arca ◽  
Lorenzo Tagliazucchi ◽  
...  

Combining drugs represent an approach to efficiently prevent and overcome drug resistance and to reduce toxicity; yet it is a highly challenging task, particularly if combinations of inhibitors of the same enzyme target are considered. To show that crystallographic and inhibition kinetic information can provide indicators of cancer cell growth inhibition by combinations of two anti-human thymidylate synthase (hTS) drugs, we obtained the X-ray crystal structure of the hTS:raltitrexed:5-fluorodeoxyuridine monophosphate (FdUMP) complex. Its analysis showed a ternary complex with both molecules strongly bound inside the enzyme catalytic cavity. The synergistic inhibition of hTS and its mechanistic rationale were consistent with the structural analysis. When administered in combination to A2780 and A2780/CP ovarian cancer cells, the two drugs inhibited ovarian cancer cell growth additively/synergistically. Together, these results support the idea that X-ray crystallography can provide structural indicators for designing combinations of hTS (or any other target)-directed drugs to accelerate preclinical research for therapeutic application.


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