We have previously reported that a redox-silent analogue of
alpha-tocotrienol (T3),
6-O-carboxypropyl-alpha-tocotrienol (T3E) shows more potential anti-carcinogenic property than T3 in a
lung cancer cell (A549 cell). However, the mechanisms by which T3E exerts its potential
anti-carcinogenic effect is still unclear. As
tumor malignancy is associated with
hypoxia adaptation, in this study, we examined whether T3E could suppress survival and invasion in A549 cells under
hypoxia.
Hypoxia treatment drastically-induced activation of the
protein tyrosine kinase, Src, and its regulated signaling required for
hypoxia adaptation of A549
tumor cells. The survival and invasion capacity of the
tumor cells under
hypoxia was suppressed by T3E via the inactivation of Src. More specifically, T3E-dependent inhibition of Src-induced Akt activation contributed to suppression of cell survival under
hypoxia, and the reduction of fibrinolytic factors such as
plasminogen activator-1(PAI-1) via the decrease of
hypoxia-inducible factor-2alpha by T3E led to inhibition of hypoxic invasion. Overall these results suggest that T3E suppresses
hypoxia adaptation of A549 cells by the inhibition in
hypoxia-induced activation of Src signaling.