Document Detail

PX-12 induces apoptosis in Calu-6 cells in an oxidative stress-dependent manner.
MedLine Citation:
PMID:  25391429     Owner:  NLM     Status:  Publisher    
PX-12 (1-methylpropyl 2-imidazolyl disulfide) as a thioredoxin (Trx) inhibitor has an anti-tumor effect. However, there is no report about the toxicological effect of PX-12 on lung cancer cells. Here, we investigated the anti-growth effects of PX-12 on Calu-6 lung cancer cells in relation to reactive oxygen species (ROS) and glutathione (GSH) levels. PX-12 induced the growth inhibition of Calu-6 cells with IC50 of nearly 3 μM at 72 h. In contrast, PX-12 did not affect the growth of human small airway epithelial cells (HSAECs). Cell cycle distribution analysis indicated that PX-12 significantly induced a G2/M phase arrest in Calu-6 cells. PX-12 also increased the number of annexin V-FITC-positive cells in Calu-6 cells. All the tested caspase inhibitors markedly prevented Calu-6 cell death induced by PX-12. With regard to ROS and GSH levels, PX-12 increased ROS levels containing O2 (·-) in Calu-6 cells and induced the depletion of GSH. N-acetyl cysteine (NAC), which is a well-known antioxidant, significantly reduced O2 (·-) level in PX-12-treated Calu-6 cells and prevented apoptosis and GSH depletion in these cells. In conclusion, it is the first report that PX-12 inhibited the growth of Calu-6 cells via a G2/M phase arrest as well as apoptosis, which effect was related to the intracellular increases in ROS levels.
Bo Ra You; Hye Rim Shin; Bo Ram Han; Woo Hyun Park
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2014-11-13
Journal Detail:
Title:  Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine     Volume:  -     ISSN:  1423-0380     ISO Abbreviation:  Tumour Biol.     Publication Date:  2014 Nov 
Date Detail:
Created Date:  2014-11-13     Completed Date:  -     Revised Date:  2014-11-14    
Medline Journal Info:
Nlm Unique ID:  8409922     Medline TA:  Tumour Biol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
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