**7.4 Tocotrienols in lung cancer**

In pulmonary carcinomas, the various tocotrienol isoforms may potentially be acknowledged as the new interventional alternatives for the successful management of the disease. In order to substantiate this claim, a previous study had suggested that all of the tocotrienol isoforms convincingly induced apoptosis in lung carcinoma cells through the activation of caspase-8 and mitochondrial cytochrome c release [17, 90]. Anticarcinogenic activity towards pulmonary carcinomas exerted by delta-tocotrienol was also achieved by raising the levels of microRNA, miR-34a, which subsequently suppressed the levels of Notch-1 and its downstream targets i.e., Bcl-2, cyclin D1, and survivin [91]. 6-O-carboxypropyl-alpha-tocotrienol, which is an analogue of alpha-tocotrienol, has been found to exhibit more potent anticarcinogenic activity in A549 lung carcinomatous cells [92, 93]. In addition, past research had suggested that tocotrienols inhibited lung carcinoma cells adaptation of hypoxic conditions by inhibiting Src-induced Akt activation, as well as through reducing HIF-2a levels [92]. Tocotrienols had also been claimed to induce apoptosis in human pulmonary adenocarcinoma that contained Ras mutation [93]. Additionally, a recent study showed that delta-tocotrienol inhibited glutamine uptake in non-small-cell lung cancer (NSCLC) cell lines A549 and H1229, which subsequently triggered the inhibition of cellular proliferation and induction of apoptosis via downregulation of the mTOR pathway [130].
