| Boswellic acid induces epigenetic alterations by modulating DNA methylation in colorectal cancer cells. | |
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MedLine Citation:
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PMID: 22415137 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Accumulating evidence suggests that chemopreventive effects of some dietary polyphenols may in part be mediated by their ability to influence epigenetic mechanisms in cancer cells. Boswellic acids, derived from the plant Boswellia serrata, have long been used for the treatment of various inflammatory diseases due to their potent anti-inflammatory activities. Recent preclinical studies have also suggested that this compound has anti-cancer potential against various malignancies. However, the precise molecular mechanisms underlying their anti-cancer effects remain elusive. Herein, we report that boswellic acids modulate DNA methylation status of several tumor suppressor genes in colorectal cancer (CRC) cells. We treated RKO, SW48 and SW480 CRC cell lines with the active principle present in boswellic acids, acetyl-keto-β-boswellic acid (AKBA). Using genome-wide DNA methylation and gene expression microarray analyses, we discovered that AKBA induced a modest genome-wide demethylation that permitted simultaneous re-activation of the corresponding tumor suppressor genes. The quantitative methylation-specific PCR and RT-PCR validated the gene demethylation and re-expression in several putative tumor suppressor genes including SAMD14 and SMPD3. Furthermore, AKBA inhibited DNMT activity in CRC cells. Taken together, these results lend further support to the growing notion that anti-cancer effect of boswellic acids may in part be due to its ability to demethylate and reactivate methylation-silenced tumor suppressor genes. These results suggest that not only boswellic acid might be a promising epigenetic modulator in the chemoprevention and treatment of CRC, but also provide a rationale for future investigations on the usefulness of such botanicals for epigenetic therapy in other human malignancies. |
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Authors:
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Yan Shen; Masanobu Takahashi; Hyang-Min Byun; Alexander Link; Nupur Sharma; Francesc Balaguer; Hon-Chiu E Leung; C Richard Boland; Ajay Goel |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2012-05-01 |
Journal Detail:
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Title: Cancer biology & therapy Volume: 13 ISSN: 1555-8576 ISO Abbreviation: Cancer Biol. Ther. Publication Date: 2012 May |
Date Detail:
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Created Date: 2012-07-19 Completed Date: 2012-12-14 Revised Date: 2013-05-02 |
Medline Journal Info:
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Nlm Unique ID: 101137842 Medline TA: Cancer Biol Ther Country: United States |
Other Details:
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Languages: eng Pagination: 542-52 Citation Subset: IM |
Affiliation:
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GI Cancer Research Laboratory, Charles A. Sammons Cancer Center and Baylor Research Institute, Baylor University Medical Center, Dallas, TX, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Anti-Inflammatory Agents
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pharmacology Apoptosis / drug effects Cell Line, Tumor Cell Proliferation / drug effects Cell Survival / drug effects Colorectal Neoplasms / genetics*, metabolism CpG Islands / drug effects DNA (Cytosine-5-)-Methyltransferase / antagonists & inhibitors DNA Methylation* Epigenesis, Genetic / drug effects* Gene Expression Profiling Gene Expression Regulation, Neoplastic / drug effects Humans Promoter Regions, Genetic Signal Transduction / drug effects Triterpenes / pharmacology* |
| Grant Support | |
ID/Acronym/Agency:
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CA129286/CA/NCI NIH HHS; R01 CA72851/CA/NCI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Anti-Inflammatory Agents; 0/Triterpenes; 631-69-6/boswellic acid; EC 2.1.1.37/DNA (Cytosine-5-)-Methyltransferase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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