Cinnamomum verum ingredient 2-methoxycinnamaldehyde: a new antiproliferative drug targeting topoisomerase I and II in human lung squamous cell carcinoma NCI-H520 cells

Cinnamomum verum has been used as a Chinese herbal medication. We investigated the antiproliferative effect of 2-methoxycinnamaldehyde (2-MCA), a constituent of the cortex of the plant, and the molecular biomarkers associated with tumorigenesis in human lung squamous cell carcinoma NCI-H520 cells. The effects of 2-MCA on cell growth, cytotoxicity, Apoptosis, and Topoisomerase I and II activities in human lung squamous cell carcinoma NCI-H520 cells were evaluated in vitro and in vivo. The results showed that 2-MCA inhibited proliferation and induced Apoptosis as implicated by mitochondrial membrane potential (ΔΨm) loss, activation of both Caspase 3 and Caspase 9, as well as morphological characteristics of Apoptosis. Furthermore, 2-MCA also induced lysosomal vacuolation with elevated volume of acidic compartment and cytotoxicity, and inhibited Topoisomerase I as well as II activities. Additional study showed the antiproliferative effect of 2-MCA in a nude mice model. In short, our data imply that the antiproliferative activity of 2-MCA in vitro involved downregulation of cell growth markers, both Topoisomerase I and II, and upregulation of proapoptotic molecules, associated with increased lysosomal vacuolation. In vivo, 2-MCA reduced the tumor size, which could have had a significant clinical impact. Our data imply that 2-MCA may be a potential agent for chemoprevention as well as Anticancer therapy.