Kaempferol modulates the metastasis of human non-small cell lung cancer cells by inhibiting epithelial-mesenchymal transition

Abstract

Research ArticleKaempferol modulates the metastaKaempferol modulates the metastaKaempferol modulates the metastasis of human non sis of human non sis of human non---small cell lung small cell lung small cell lung cancer cells by inhibiting epithelial cancer cells by inhibiting epithelial cancer cells by inhibiting epithelial---mesenchymal transition mesenchymal transition mesenchymal transition BJP IntroductionLung cancer is the most commonly diagnosed cancer type worldwide and a leading cause of cancer-related deaths. It can be categorized into two sub-types: nonsmall cell lung cancer (Koh et al., 2012) and small cell lung cancer. Despite many efforts to improve lung cancer outcome, long-term survival has not improved significantly over the last 20 years, with a 5-year cumulative survival rate that remains very dismal at only 15% (Ghosal et al., 2009). Current standard therapies limited to chemotherapy and radiotherapy or both rarely cure this disease, thus accentuating the need for more effective and alternate therapeutic strategies.Metastasis is a complex, multistep process and involves the invasion of cells from primary tumors into the circulation, migration to distant organs and finally infiltration into tissues referred to as secondary metastatic sites (Gupta and Massagué, 2006). Epithelial-mesenchymal transition (EMT), a developmental program plays an important role in this process and involves downregulation of epithelial markers like E-cadherin and upregulation of mesenchymal markers like vimentin and fibronectin (Borthwick et al., 2009;Kalluri and Neilson, 2003). As a result, the epithelial cells acquire fibroblastlike properties, thus losing their defined cell-cell and cell-extracellular matrix contacts (Thiery et al., 2010). Thus, the EMT becomes a target to prevent tumor progression.Flavonoids are polyphenolic natural compounds present in a wide variety of fruits and vegetables (Bosetti et al., 2007) and in recent years their anti-tumor activities have been widely studied and recognized (Gonzalez and Riboli, 2006). Kaempferol (3,4',5,7-tetrahydroxyflavone), is a natural polyphenol of the flavonoid family and exhibits various biological properties including anti -tumor activities. It induces apoptosis and cell cycle arrest in various cancer cell lines, including lung cancer cells (Nguyen et al., 2003), breast cancer cells (Kang et al., 2010), colon cancer cells (Li et al., 2009), besides inhibiting the migration and invasiveness of glioma cells (Shen et al., 2006). The effect of kaempferol on the growth and invasiveness of lung cancer is not yet determined and the mechanism involved needs to be defined. The present study examined the effects of kaempferol on the metastasis and invasion of A549 non-small cell lung cancer cells. It was found that kaempferol markedly inhibited cell proliferation besides overcoming EMT and cell migration. AbstractThe present study was done to determine whether kaempferol, a natural polyphenol of the flavonoid family, affects Epithelial-Mesenchymal Transition (EMT) in no...

Kaempferol – A dietary anticancer molecule with multiple mechanisms of action: Recent trends and advancements

“…In another study, KMF suppressed the transforming growth factor-b1 (TGF-b1) induced human non-small cell lung cancer (NSCLC, A549) transition from epithelial-to-mesenchymal (EMT) and migration by abolishing Akt1-mediated Smad3 phosphorylation (Eunji, Park, Choi, Jeon, & Kim, 2015). Correspondingly, Hang, Zhao, Chen, Sun, and Zhang (2015) observed the modulation of EMT-cognate proteins, including E-cadherin and vimentin in KMF-treated non-minuscule lung cancer cells (Hang et al, 2015).…”

Therapeutic effects of medicinal plants and their constituents on lung cancer, in vitro, in vivo and clinical evidence

“…Kaempferol treatment (25 μM) for 48 h also decreased the expression of GST, NQO1 and HO1, triggered Nrf2 by tert‐butylhydroquinone (tBHQ), reduced ROS levels and induced apoptosis in treated cells 146 . Finally, Hang et al 147 found various doses of kaempferol (20, 40, 60, 80, 100, 120 and 140 μM) reduced migration and metastasis of cells, induced cell mortality and apoptosis and modulated EMT protein expression in human NSCLC cells. These results suggest that the anti‐cancer mechanisms of A. millefolium and its constituent kaempferol are broad and lead to cancer cell immobility and death.…”

“…There are several in vitro and even in vivo studies that found A. millefolium, C. longa, Ferula spp., N. sativa and their constituents reduced lung cancer cell migration 44,58,81,91,130,143 and lung cancer metastasis. 58,81,112,125,147 The effects of these natural products on migration and metastasis of lung cancer are shown in Figure 2.…”