Epigenetic Therapy as a Potential Approach for Targeting Oxidative Stress–Induced Non-Small-Cell Lung Cancer

2021 ◽  
pp. 1-16
Author(s):  
Ridhima Wadhwa ◽  
Keshav Raj Paudel ◽  
Shakti Shukla ◽  
Madhur Shastri ◽  
Gaurav Gupta ◽  
...  
2021 ◽  
pp. 1-16
Author(s):  
Ridhima Wadhwa ◽  
Keshav Raj Paudel ◽  
Shakti Shukla ◽  
Madhur Shastri ◽  
Gaurav Gupta ◽  
...  

Cancers ◽  
2018 ◽  
Vol 10 (4) ◽  
pp. 126 ◽  
Author(s):  
Christophe Deben ◽  
Vanessa Deschoolmeester ◽  
Jorrit De Waele ◽  
Julie Jacobs ◽  
Jolien Van den Bossche ◽  
...  

The compound APR-246 (PRIMA-1MET) is a known reactivator of (mutant) p53 and inducer of oxidative stress which can sensitize cancer cells to platinum-based chemotherapeutics. However, the effect of a hypoxic tumor environment has been largely overlooked in this interaction. This study focusses on the role of hypoxia-inducible factor-1α (HIF-1α) and the p53 tumor suppressor protein in hypoxia-induced cisplatin resistance in non-small cell lung cancer (NSCLC) cells and the potential of APR-246 to overcome this resistance. We observed that hypoxia-induced cisplatin resistance only occurred in the p53 mutant NCI-H2228Q331* cell line, and not in the wild type A549 and mutant NCI-H1975R273H cell lines. Cisplatin reduced HIF-1α protein levels in NCI-H2228Q331* cells, leading to a shift in expression from HIF-1α-dependent to p53-dependent transcription targets under hypoxia. APR-246 was able to overcome hypoxia-induced cisplatin resistance in NCI-H2228Q331* cells in a synergistic manner without affecting mutant p53Q331* transcriptional activity, but significantly depleting total glutathione levels more efficiently under hypoxic conditions. Synergism was dependent on the presence of mutant p53Q331* and the induction of reactive oxygen species, with depletion of one or the other leading to loss of synergism. Our data further support the rationale of combining APR-246 with cisplatin in NSCLC, since their synergistic interaction is retained or enforced under hypoxic conditions in the presence of mutant p53.


2017 ◽  
Vol 2017 ◽  
pp. 1-8 ◽  
Author(s):  
Sameera R. Samarakoon ◽  
Meran K. Ediriweera ◽  
Chukwumaobim Daniel Uzochukwuwulu Nwokwu ◽  
Chamara Janaka Bandara ◽  
Kamani H. Tennekoon ◽  
...  

Lung cancer is the major cause of cancer death among men. A number of natural compounds have proven to be useful in the treatmet of lung cancer. This study was aimed to determine cytotoxic and apoptotoic effects of a natural compound 3-O-α-L-arabinosyl oleanolic acid (3-O-L-AO) isolated fromSchumacheria castaneifoliain non-small-cell lung cancer (NCI-H292) cells. Cytotoxic effects of 3-O-L-AO were determined by Sulforhodamine B (SRB) assay and apoptotic effects were tested by evaluating (a) apoptotsis related morphological changes, (b) caspase 3/7 activity, and (c) expression ofBax, p53, and survivingenes. Oxidative stress markers (reactive oxygen species (ROS), glutathione-S-transferase (GST), and glutathione (GSH)) were also analysed in 3-O-L-AO treated NCI-H292 cells. 3-O-L-AO exerted potent cytotoxic effects in NCI-H292 cells while being less cytotoxic to normal lung (MRC-5) cells. Exposure to 3-O-L-AO caused upregulation ofBaxandp53and downregulation ofsurvivinin NCI-H292 cells. Activation of caspase 3/7 and morphological features related to apoptosis further confirmed 3-O-L-AO induced apoptosis. Furthermore, elevated ROS and GST levels and decreased GSH levels suggested 3-O-L-AO can induce apoptosis, possibly causing oxidative stress in NCI-H292 cells. Overall results suggest that 3-O-L-AO can be considered as an effective anticancer agent for the treatment of lung cancer.


Epigenetics ◽  
2016 ◽  
Vol 11 (12) ◽  
pp. 858-870 ◽  
Author(s):  
Insa Schiffmann ◽  
Gabriele Greve ◽  
Manfred Jung ◽  
Michael Lübbert

Oncotarget ◽  
2016 ◽  
Vol 7 (42) ◽  
pp. 68768-68780 ◽  
Author(s):  
Shirong Zhang ◽  
Kan Wu ◽  
Jianguo Feng ◽  
Zhibing Wu ◽  
Qinghua Deng ◽  
...  

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