Delta-tocotrienol augments cisplatin-induced suppression of non-small cell lung cancer cells via inhibition of the Notch-1 pathway.

Xiangming Ji, Zhiwei Wang, Fazlul H Sarkar, Smiti V Gupta

Index: Anticancer Res. 32(7) , 2647-55, (2012)

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Abstract

Non-small cell lung cancer (NSCLC), accounting for 80% of lung cancers, is the leading cause of all cancer deaths. Previously, we demonstrated that delta-tocotrienol inhibits 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, could enhance the anticancer effects of cisplatin. Treatment with a combination of delta-tocotrienol and cisplatin resulted in a dose-dependent, significant inhibition of cell growth, migration, invasiveness, and induction of apoptosis in NSCLC cells, as compared to the single agents. This was associated with a decrease in NF-κB DNA binding activity, decrease in Notch-1, Hes-1, Bcl-2 and increase in cleaved Caspase-3 and PARP expressions. These results suggest that down-regulation of Notch-1, via inhibition of NF-κB signaling pathways by delta-tocotrienol and cisplatin, in combination, could provide a potential novel approach for tumor arrest in NSCLC, while lowering the effective dose of cisplatin.