Inhibitory effect of apigenin against migration and invasion of human lung cancer A549 cells and the related mechanism

Eupolyphaga sinensis Walker is an important insect used in Chinese traditional medicine. In this study, we purified a 72-kDa anticancer protein, designated as EPS72, from this species using ammonium sulfate precipitation, ultrafiltration, CM Sepharose Fast Flow cation exchange, Q Sepharose High Performance (HP) anion exchange, Butyl Sepharose HP hydrophobic chromatography, and Superdex 75 gel filtration chromatographic techniques. EPS72 exhibited a potent anticancer activity against the human lung cancer A549 cell line (IC50, 18.76 μg/mL). Further study showed that EPS72 could induce A549 cell detachment and apoptosis, inhibit cell adhesion to fibronectin and collagen IV, and restrain cell migration and invasion. Moreover, EPS72 significantly decreased the expression of β1-integrin. This study suggests that EPS72 could potentially be developed as a novel anticancer therapeutic agent due to its possible antimetastatic activity.

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Cyclic pentapeptide cRGDfK enhances the inhibitory effect of sunitinib on TGF-β1-induced epithelial-to-mesenchymal transition in human non-small cell lung cancer cells

10.1101/2020.04.27.063776 ◽

2020 ◽

Author(s):

Kyeong-Yong Park ◽

Jiyeon Kim

Keyword(s):

Lung Cancer ◽

Wnt Signaling ◽

Cancer Cells ◽

Human Lung ◽

Inhibitory Effect ◽

Lung Cancer Cells ◽

Human Lung Cancer ◽

Migration And Invasion ◽

Mesenchymal Transition ◽

Tgf Β1

AbstractIn human lung cancer progression, the EMT process is characterized by the transformation of cancer cells into invasive forms that migrate to other organs. Targeting to EMT-related molecules is emerging as a novel therapeutic approach for the prevention of lung cancer cell migration and invasion. Traf2- and Nck-interacting kinase (TNIK) has recently been considered as an anti-proliferative target molecule to regulate the Wnt signaling pathway in several types of cancer cells. In the present study, we evaluated the inhibitory effect of a tyrosine kinase inhibitor sunitinib and the integrin-αVβ3 targeted cyclic peptide (cRGDfK) on EMT in human lung cancer cells. Sunitinib strongly inhibited the TGF-β1-activated EMT through suppression of Wnt signaling, Smad and non-Smad signaling pathways. In addition, the cRGDfK also inhibited the expression of TGFβ1-induced mesenchymal marker genes and proteins. The anti-EMT effect of sunitinib was enhanced when cRGDfK was treated together. When sunitinib was treated with cRGDfK, the mRNA and protein expression levels of mesenchymal markers were decreased compared to the treatment with sunitinib alone. Co-treatment of cRGDfK has shown the potential to improve the efficacy of anticancer agents in combination with therapeutic agents that may be toxic at high concentrations. These results provide new and improved therapies for treating and preventing EMT-related disorders, such as lung fibrosis and cancer metastasis, and relapse.

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