Delta‐Tocotrienol enhances cisplatin‐induced inhibition of growth and invasion of Non‐Small Cell Lung Cancer Cells

Lung cancer is the leading cause of death among all cancers. Non‐small cell lung cancer (NSCLC) accounts for 80% of lung cancer with a five‐year survival rate of 16%. Although a subset of NSCLC patients benefit from the development of target therapies, cisplatin remains the standard chemotherapeutic drug. Previously, we demonstrated that delta‐tocotrienolinhibits NSCLC cell proliferation, invasion and induces apoptosis by down‐regulation of the Notch‐1 signaling pathway. The objective of this study was to investigate whether delta‐tocotrienol, a naturally occurring isoform of Vitamin E, could enhance the cisplatin‐induced inhibition of growth and invasion of NSCLCcells. Treatment of NSCLCcells with delta‐tocotrienoland cisplatin in combination resulted in a dose dependent inhibition of cell growth, cell migration, tumor cell invasiveness, and induction of apoptosis in NSCLC cells. Real‐time RT‐PCR and western blot analysis showed that antitumor activity by the combination of delta‐tocotrienol and cisplatin was associated with decreases in Notch‐1, Hes‐1, Survivin, and Bcl‐XLand increases in cleaved PARP, Caspase‐3 expressions. In addition, there was a decrease in NF‐κB‐DNA binding activity. These results suggest that down‐regulation of Notch‐1, via inhibition of NF‐κB signaling pathways by delta‐tocotrienol and cisplatin, could provide a potential novel approach for prevention of tumor progressionin non‐small cell lung cancer. This research was supported by funds provided by Wayne State University. Grant Funding Source : Wayne State University