Novel anti-cancer agent myrtucommulone-A and thymoquinone abrogate epithelial–mesenchymal transition in cancer cells mainly through the inhibition of PI3K/AKT signalling axis

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• 作者：Banu Iskender ; Kenan Izgi ; Halit Canatan
• 刊名：Molecular and Cellular Biochemistry
• 出版年：2016
• 出版时间：May 2016
• 年：2016
• 卷：416
• 期：1-2
• 页码：71-84
• 全文大小：8,574 KB
• 刊物类别：Biomedical and Life Sciences
• 刊物主题：Life Sciences
  Biochemistry
  Medical Biochemistry
  Oncology
  Cardiology
  
• 出版者：Springer Netherlands
• ISSN：1573-4919
• 卷排序：416

文摘

Epithelial–mesenchymal transition (EMT) plays a prominent role in cancer progression and metastasis. Inhibition of EMT-associated regulators may hold a huge promise for cancer therapy. Although TGF-β signalling has a pivotal role in the induction of EMT, alterations during the EMT process are usually initiated and controlled by the cross-talk of multiple signalling pathways, and in most cases this is context-dependent. In the present study, we aimed at identifying the molecular mechanisms during the inhibition of EMT by novel anti-cancer agent myrtucommulone-A (MC-A) and thymoquinone (TQ). We used epithelial cancer cells to study the effects of MC-A and TQ on EMT. We first showed the functional inhibition of EMT by MC-A or TQ using migration assays and confirmed the EMT inhibition by analysing the expression of EMT markers with RT-PCR, immunocytochemistry and Western blotting. We evaluated the changes in intracellular dynamics by Western blotting and compared the effects of MC-A and TQ with the effects of selective inhibitors of PI3K (LY294002), ERK 1/2 (U0126) and TGF-βR (SB431542). We demonstrate that both MC-A and TQ treatment negatively regulate the EMT process through modulation of signalling pathways in cancer cells. MC-A and TQ treatment inhibited phosphorylation of multiple proteins in a context-dependent manner. Novel anti-cancer agent MC-A and TQ regulate distinct signalling pathways for the repression of EMT which emphasises the significance of combinational therapies in cancer treatment. MC-A and TQ could be considered as candidate molecules for combinational therapies with their ability to interfere signalling pathways regulating cancer cell behaviour.KeywordsEpithelial cancer cellsHTB-9MDA-MB-231Epithelial–mesenchymal transitionPI3K/AKT pathwayMyrtucommulone-AThymoquinone