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Inhibition of cell growth and induction of apoptosis in non‐small cell lung cancer cells by delta‐tocotrienol is associated with notch‐1 down‐regulation
Author(s) -
Ji Xiangming,
Wang Zhiwei,
Geamanu Andreea,
Sarkar Fazlul H,
Gupta Smiti V
Publication year - 2011
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.23184
Subject(s) - survivin , notch signaling pathway , apoptosis , cancer research , cell growth , lung cancer , biology , cell , notch 1 , programmed cell death , signal transduction , microbiology and biotechnology , medicine , biochemistry
Lung cancer is the leading cause of death among all cancers. Non‐small cell lung cancer accounts for 80% of lung cancer with a 5‐year survival rate of 16%. Notch pathway, especially Notch‐1 is up‐regulated in a subgroup of non‐small cell lung cancer patients. Since Notch‐1 signaling plays an important role in cell proliferation, differentiation, and apoptosis, down‐regulation of Notch‐1 may exert anti‐tumor effects. The objective of this study was to investigate whether delta‐tocotrienol, a naturally occurring isoform of Vitamin E, inhibits non‐small cell lung cancer cell growth via Notch signaling. Treatment with delta‐tocotrienol resulted in a dose and time dependent inhibition of cell growth, cell migration, tumor cell invasiveness, and induction of apoptosis. Real‐time RT‐PCR and western blot analysis showed that antitumor activity by delta‐tocotrienol was associated with a decrease in Notch‐1, Hes‐1, Survivin, MMP‐9, VEGF, and Bcl‐XL expression. 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, could provide a potential novel approach for prevention of tumor progression in non‐small cell lung cancer. J. Cell. Biochem. 112: 2773–2783, 2011. © 2011 Wiley‐Liss, Inc.