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Synthetic Triterpenoid Cyano Enone of Methyl Boswellate (CEMB) activates intrinsic, extrinsic & endoplasmic reticulum stress cell death pathways in tumor cell lines.
MedLine Citation:
PMID:  21746806     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
We explored the effect of a novel synthetic triterpenoid compound Cyano Enone of Methyl Boswellates (CEMB) on various prostate cancer and glioma cancer cell lines. CEMB displayed concentration-dependent cytotoxic activity with submicromolar lethal dose 50% (LD50) values in ten of ten tumor cell lines tested. CEMB induced cytotoxicity is accompanied by activation of downstream effector caspases (caspases 3 and 7) and by upstream initiator caspases involved in both the extrinsic (caspase 8) and intrinsic (caspase 9) apoptotic pathways. By using small interfering RNAs (siRNAs), we show evidence that knock down of caspase 8, DR4, Apaf-1, and Bid impairs CEMB induced cell death. Similar to other pro-apoptotic synthetic triterpenoid compounds, CEMB induced apoptosis involved endoplasmic reticulum (ER) stress, as demonstrated by partial rescue of tumor cells by siRNA mediated knock down of expression of genes involved in the unfolded protein response such as IRE1α, PERK, and ATF6. Altogether our results suggest that CEMB stimulates several apoptotic pathways in cancer cells, suggesting that this compound should be evaluated further as a potential agent for cancer therapy.
Authors:
Palaniyandi Ravanan; Renata Sano; Talwar Priti; Satoshi Ogasawara; Shu-Ichi Matsuzawa; Michael Cuddy; Sanjay K Singh; G S R Subba Rao; Paturu Kondaiah; John C Reed
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-7-11
Journal Detail:
Title:  Molecular cancer therapeutics     Volume:  -     ISSN:  1538-8514     ISO Abbreviation:  -     Publication Date:  2011 Jul 
Date Detail:
Created Date:  2011-7-12     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101132535     Medline TA:  Mol Cancer Ther     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
1Cancer Center, Sanford-Burnham Medical Research Institute.
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