Document Detail

PARP cleavage and perturbance in mitochondrial membrane potential by 3-α-propionyloxy-β-boswellic acid results in cancer cell death and tumor regression in murine models.
MedLine Citation:
PMID:  22830406     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: Apoptotic induction in cancer cells has become a major focus of anticancer therapeutics. In this regard, β-boswellic acids, naturally occurring pentacyclic triterpenes, have demonstrated antiproliferative and cytotoxic effects against different types of cancers. Surprisingly, not much has been reported regarding the chemical modifications or preparation of structural analogs of the key constituents of β-boswellic acid.
AIM: The anticancer activity of 3-α-propionyloxy-β-boswellic acid (POBA) was investigated and this article reports for the first time that the triterpenoid ring of the boswellic acid derivative POBA is targeting the PI3K pathway.
MATERIALS & METHODS: Induction of apoptosis of the semi-synthetic derivative of β-boswellic acid-POBA in vitro was analyzed using a battery of human cancer cell lines followed by cell cycle phase distribution, further validated by DNA fragmentation, and was found to cause mitochondrial membrane potential loss with ultrastructural changes, as observed by electron microscopy studies and expression study using PARP cleavage, as well as validated by in vivo anti-tumor activity.
RESULTS: The cytotoxicity data revealed the sensitivity of various human cancer cell lines of varied tissue origin to β-boswellic acid, which robustly induced cell cycle arrest, DNA fragmentation and loss of mitochondrial membrane potential. Morphological studies of the effects of POBA revealed loss of surface projections, chromatin condensation, apoptotic body formation and POBA-mediated PARP cleavage. For in vivo therapeutic experiments, murine tumor models were treated with POBA and the treatment resulted in a significantly higher level of growth inhibition and apoptosis was significantly induced.
CONCLUSION: These findings demonstrate that acyl substituents/groups in the main skeleton of β-boswellic acid have the potential to be potent chemotherapeutic agents.
Yasrib Qurishi; Abid Hamid; Parduman R Sharma; Zahoor Ahmad Wani; Dilip M Mondhe; Shashank K Singh; Mohmmad Afzal Zargar; Samar S Andotra; Bhahwal Ali Shah; Subhash C Taneja; Ajit Kumar Saxena
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Future oncology (London, England)     Volume:  8     ISSN:  1744-8301     ISO Abbreviation:  Future Oncol     Publication Date:  2012 Jul 
Date Detail:
Created Date:  2012-07-26     Completed Date:  2013-02-12     Revised Date:  2014-07-31    
Medline Journal Info:
Nlm Unique ID:  101256629     Medline TA:  Future Oncol     Country:  England    
Other Details:
Languages:  eng     Pagination:  867-81     Citation Subset:  IM    
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MeSH Terms
Antineoplastic Agents, Phytogenic / pharmacology*
Apoptosis / drug effects
Body Weight / drug effects
Carcinoma, Ehrlich Tumor / drug therapy,  pathology
Cell Death / drug effects
Cell Line, Tumor
Drug Screening Assays, Antitumor
HL-60 Cells
Inhibitory Concentration 50
Membrane Potential, Mitochondrial / drug effects*
Molecular Structure
Phosphatidylinositol 3-Kinases / antagonists & inhibitors,  metabolism
Poly(ADP-ribose) Polymerases / metabolism*
Triterpenes / chemical synthesis,  chemistry,  pharmacology*
Reg. No./Substance:
0/3-alpha-propionyloxy-beta-boswellic acid; 0/Antineoplastic Agents, Phytogenic; 0/Triterpenes; 631-69-6/boswellic acid; EC Polymerases; EC 2.7.1.-/Phosphatidylinositol 3-Kinases

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