A novel anticancer chromeno-pyrimidine analogue inhibits epithelial-mesenchymal transition in lung adenocarcinoma cells.

ABSTRACT

Cancer is the second most dreaded disease worldwide. It is either acquired or inherited leading to the accompanying undesirable changes in the affected cells. Most existing chemotherapeutic drugs show enormous side effects. To minimize such effects, constant progress has been observed in the field of cancer by screening the anti-cancer effects of different chemical analogues. In the current study, we investigated the mechanism of action of a novel anticancer chromeno-pyrimidine analogue. We employed MTT, LDH assay to study cytotoxicity. DNA fragmentation, fluorescence imaging, and flow cytometric techniques have been carried out to study apoptosis, ROS generation, and cell cycle respectively. Wound healing assay and western blotting were used to evaluate the markers of epithelial-mesenchymal transition associated with metastasis. Molecular docking was used to predict possible protein targets that bind to this compound. The novel analogue induced apoptosis in lung adenocarcinoma cells and exhibited anti-metastatic activity. Increased expression of E-cadherin and inhibition of epithelial-mesenchymal transition was also observed. Docking studies with metastasis-related proteins such as Frizzled-7 (CRD), and Snail1 predict a high binding affinity of CP4b to both proteins. The novel analogue is therefore an anti-metastatic compound with EMT-inhibiting property and is hypothesized to act via binding to multiple targets in cancer cells.