| Curcumin: a novel Stat3 pathway inhibitor for chemoprevention of lung cancer. | |
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MedLine Citation:
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PMID: 22156994 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Multiple studies from independent groups find evidence for signal transducer and activator of transcription 3 (Stat3) activation in nearly 50% of lung cancers, suggesting a functional role for this target in subsets of lung cancer. On the basis of the existing evidence, we hypothesized that bioavailable curcuminoid complex may modulate lung carcinogenesis, primarily by inhibiting Stat3 activation. With the safety of this being botanically well established, the objective of these studies was to test our hypothesis in vitro and in vivo in an effort to inform the design of a phase II chemoprevention trial in former smokers. We treated non-tumor-derived, normal (but immortalized) human bronchial epithelial cells (AALE) (Lundberg et al., 2002; Pillai et al., 2011) and lung adenocarcinoma-derived cells (H441) with bioactive curcumin C3 complex. Asynchronous cells in each case were treated with curcumin for 24 h, followed by immunoblotting for Stat3 and activated Stat3-P, prior signal of which was used for normalization. We also completed a preclinical trial in which 12 mice were randomly divided into three groups and subjected to 3 days or 9 days of curcumin intraperitoneal injections, followed by analysis of lung tissues for Stat3-P changes and growth suppressive effects of the curcumin. The growth suppressive effects were measured using Cyclin D1 and the replicative helicase subunit, Mcm2, as surrogates for the proliferative capacity of the tissues. In-vitro studies with curcuminoid complex demonstrated that the activity of Stat3 in both normal bronchoepithelial cells and lung cancer-derived cells is sensitive to curcumin exposure. In a dose-dependent manner, curcumin treatment resulted in significant suppression of Stat3 phosphorylation and reduction in the proliferative capacity of both cell types. In the preclinical trial with rodent models, curcumin reduced Stat3-P and the proliferative markers CycD1 and Mcm2 in mice lung tissues in vivo. These culture and preclinical studies indicate that the activity of the Stat3 pathway can be suppressed by curcumin treatment, concomitant with a reduction in cell proliferation, supporting our hypothesis that inhibition of the Stat3 pathway represents at least one important mechanism by which curcumin elicits its effects on the bronchoepithelium. These data provide a rationale for the use of curcumin as a promising chemopreventive agent in high-risk populations such as former smokers. |
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Authors:
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Mark G Alexandrow; Lanxi J Song; Soner Altiok; Jhanelle Gray; Eric B Haura; Nagi B Kumar |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural |
Journal Detail:
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Title: European journal of cancer prevention : the official journal of the European Cancer Prevention Organisation (ECP) Volume: 21 ISSN: 1473-5709 ISO Abbreviation: Eur. J. Cancer Prev. Publication Date: 2012 Sep |
Date Detail:
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Created Date: 2012-07-24 Completed Date: 2012-10-23 Revised Date: 2013-04-16 |
Medline Journal Info:
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Nlm Unique ID: 9300837 Medline TA: Eur J Cancer Prev Country: England |
Other Details:
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Languages: eng Pagination: 407-12 Citation Subset: IM |
Affiliation:
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Department of Molecular Oncology, H. Lee Moffitt Cancer Center & Research Institute, University of South Florida College of Medicine, Tampa, Florida 33612, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Cell Line Curcumin / therapeutic use* Enzyme Inhibitors / therapeutic use* Female Humans Lung Neoplasms / prevention & control* Mice Mice, Nude Random Allocation STAT3 Transcription Factor / antagonists & inhibitors* |
| Grant Support | |
ID/Acronym/Agency:
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1P50-CA119997/CA/NCI NIH HHS; 1R01 CA121182/CA/NCI NIH HHS; P50 CA119997-01A2/CA/NCI NIH HHS; R01 CA121182-01A1/CA/NCI NIH HHS; R01 CA130865-01A2/CA/NCI NIH HHS; R01-CA130865/CA/NCI NIH HHS; R21-CA155393/CA/NCI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Enzyme Inhibitors; 0/STAT3 Transcription Factor; 458-37-7/Curcumin |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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