Tocotrienols suppress non‐small lung cancer cells via downregulation of the Notch‐1 signaling pathway (644.1)

Abstract

Non‐small cell lung cancer (NSCLC), accounting for 87% of all lung cancers with a 5‐year survival rate of 16%, is the leading cause for global lung cancer deaths. Tocotrienols, isomers of Vitamin E have been shown to exhibit anti‐tumor activity via inhibition of different signaling pathways in tumors. The Notch ‐1 pathway has been reported to be up regulated in lung cancer patients in vivo and in vitro studies. Therefore, the objective of this study was to investigate the interactions and effects of commercially available tocorienol isomers on the Notch‐1 pathway in adenocarcinoma (A549) and squamous cell carcinoma NSCLC (H520) cell lines. Treatment with Tocotrinols resulted in a dose dependent significant decrease in cell growth, cell migration, tumor invasiveness and induction of apoptosis. Molecular mechanisms behind these changes were explored by testing the expression of Notch‐1 and its downstream stream genes by RT‐PCR and western blot analysis. A dose dependent decrease in expression was observed in Notch‐1 and its downstream genes related to proliferation, apoptosis and invasion (Hes‐1, Survivin, PARP, MMP‐9, VEGF, Bcl 2 and Bcl‐XL). In addition, we found a mechanistic link between the Notch‐1 pathway and. NF‐kB. Thus, our data suggests that commercially available Tocotrienols inhibits cell line growth, cell migration, and tumor cell invasiveness via down regulation of Notch 1and NF‐kB pathway while inducing apoptosis, and could therefore be a potential therapeutic approach.