Title |
CDA-2, a Urinary Preparation, Inhibits Lung Cancer Development through the Suppression of NF-kappaB Activation in Myeloid Cell
|
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Published in |
PLOS ONE, December 2012
|
DOI | 10.1371/journal.pone.0052117 |
Pubmed ID | |
Authors |
Xuan Wang, Cui-Min Jiang, Hai-Ying Wan, Jun-Lu Wu, Wen-Qiang Quan, Robert Bals, Kai-Yin Wu, Dong Li |
Abstract |
CDA-2 (cell differentiation agent 2), a urinary preparation, has potent anti- proliferative and pro-apoptotic properties in cancer cells. However, the mechanisms of tumor inhibitory action of CDA-2 are far from clear, and especially there was no report on lung cancer. Here we demonstrate that CDA-2 and its main component phenylacetylglutamine (PG) reduce the metastatic lung tumor growth, and increases survival time after inoculation with Lewis lung carcinoma (LLC) cells in a dose-dependent manner in C57BL6 mice. Proliferative program analysis in cancer cells revealed a fundamental impact of CDA-2 and PG on proliferation and apoptosis, including Bcl-2, Bcl-XL, cIAP1, Survivin, PCNA, Ki-67 proteins and TUNEL assays. CDA-2 and PG significantly reduced NF-κB DNA-binding activity in lung cancer cells and in alveolar macrophages of tumor bearing mice and especially decreased the release of inflammatory factors including TNFα, IL-6, and KC. Furthermore, CDA-2 and PG decrease the expressions of TLR2, TLR6, and CD14, but not TLR1, TLR3, TLR4, and TLR9 in bone-marrow-derived macrophages (BMDM) of mice stimulated by LLC-conditioned medium (LLC-CM). Over-expressing TLR2 in BMDM prevented CDA-2 and PG from inhibiting NF-κB activation, as well as induction of TNFα and IL-6. TLR2:TLR6 complexes mediate the effect of NF-κB inactivation by CDA-2. In conclusion, CDA-2 potently inhibits lung tumor development by reduction of the inflammation in lung through suppression of NF-κB activation in myeloid cells, associating with modulation of TLR2 signaling. |
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Demographic breakdown
Readers by professional status | Count | As % |
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Professor | 2 | 12% |
Student > Ph. D. Student | 2 | 12% |
Librarian | 1 | 6% |
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Other | 2 | 12% |
Unknown | 5 | 29% |
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Agricultural and Biological Sciences | 2 | 12% |
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Engineering | 1 | 6% |
Other | 0 | 0% |
Unknown | 6 | 35% |