NDLI: Cryptopleurine targets NF-κB pathway, leading to inhibition of gene products associated with cell survival, proliferation, invasion, and angiogenesis.

Content Provider	Directory of Open Access Journals (DOAJ)
Author	Hong Ri Jin Song Zhu Jin Xing Fu Cai Donghao Li Xue Wu Ji Xing Nan Jung Joon Lee Xuejun Jin
Abstract	Cryptopleurine, a phenanthroquinolizidine alkaloid, was known to exhibit anticancer activity; however, the underlying mechanism is poorly understood. Because the nuclear factor-κB (NF-κB) transcription factors control many physiological processes including inflammation, immunity, and development and progression of cancer, we investigated the effects of cryptopleurine on tumor necrosis factor alpha (TNF-α)-induced NF-κB activation pathway and on the expression of NF-κB-regulated gene products associated with many pathophysiological processes.MDA-MB231, MDA-MB435, MCF-7, HEK293, RAW264.7 and Hep3B cells were used to examine cryptopleurine's effect on the NF-κB activation pathway. Major assays were promoter-reporter gene assay, electrophoretic mobility shift assay (EMSA), in vitro immune complex kinase assay, real-time PCR, Western blot analysis, and Matrigel invasion assay. Experiments documenting cell proliferation and apoptosis were analyzed by MTT method and flow cytometry, respectively. The results indicated that cryptopleurine suppressed the NF-κB activation through the inhibition of IκB kinase (IKK) activation, thereby blocking the phosphorylation and degradation of the inhibitor of NF-κB alpha (IκBα) and the nuclear translocation and DNA-binding activity of p65. The suppression of NF-κB by cryptopleurine led to the down-regulation of gene products involved in inflammation, cell survival, proliferation, invasion, and angiogenesis.Our results show that cryptopleurine inhibited NF-κB activation pathway, which leads to inhibition of inflammation, proliferation, and invasion, as well as potentiation of apoptosis. Our findings provide a new insight into the molecular mechanisms and a potential application of cryptopleurine for inflammatory diseases as well as certain cancers associated with abnormal NF-κB activation.
e-ISSN	19326203
DOI	10.1371/journal.pone.0040355
Journal	PLoS ONE
Issue Number	6
Volume Number	7
Language	English
Publisher	Public Library of Science (PLoS)
Publisher Date	2012-01-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Medicine Science
Content Type	Text
Resource Type	Article

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