Abstract
Lung cancer appears to have the highest rate of mortality among cancers due to its metastasis capability. To achieve metastasis, cancer cells acquire the ability to undergo a switch from epithelial to mesenchymal behaviour, termed the epithelial-to-mesenchymal transition (EMT), which is associated with poor clinical outcomes. Drug discovery attempts have been made to find potent compounds that will suppress EMT. Cypripedin, a phenanthrenequinone isolated from Thai orchid, Dendrobium densiflorum, exhibits diverse pharmacological activities. In this study, we found that cypripedin attenuated typical mesenchymal phenotypes, including migratory behaviour, of non-small cell lung cancer H460 cells, with a significant reduction of actin stress fibres and focal adhesion and with weakened anchorage-independent growth. Western blot analysis revealed that the negative activity of this compound on EMT was a result of the down-regulation of the EMT markers Slug, N-Cadherin and Vimentin, which was due to ATP-dependent tyrosine kinase (Akt) inactivation. As a consequence, the increase in the Slug degradation rate via a ubiquitin-proteasomal mechanism was encouraged. The observation in another lung cancer H23 cell line also supported this finding, indicating that cypripedin exhibits a promising pharmacological action on lung cancer metastasis that could provide scientific evidence for the further development of this compound.
Highlights
Lung cancer has become the leading cause of cancer death, and the number of deaths has been gradually increasing every year
The data are presented as mean ± SEM (n = 4). *p < 0.05 compared with untreated control cells. (C) H460 cells were treated with various concentrations (0–100 μM) of cypripedin for 72 h; apoptotic cells were investigated by Hoechst 33342 nuclear staining dye
The data are presented as mean ± SEM (n = 4). *p < 0.05 compared with control cells. (D) The cells with apoptotic nuclei are illustrated. (E) H460 cells were treated with non-toxic concentrations (0–20 μM) of cypripedin for 24, 48 and 72 h; cell growth was examined by cell proliferation assay and is presented as a relative value
Summary
Lung cancer has become the leading cause of cancer death, and the number of deaths has been gradually increasing every year. Cancer cells spread throughout the body in a series of integrated-steps, of which the transition from epithelial to mesenchymal activity plays a crucial prerequisite phase that enhances the motile ability and survival of metastatic cells[3]. These trans-differentiation features are involved in the loss of cell-cell adhesion and with the morphological change to spindle-like mesenchymal cells that are favourable for migration[4]. Since EMT is a primary process required for cancer metastasis, this study aimed to examine whether cypripedin was able to attenuate this aggressive behaviour in in vitro lung cancer cells and to examine the underlying mechanism
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