World Journal of
Pharmaceutical and Life Sciences

DELTA-TOCOTRIENOL IS THE MOST BIOACTIVE ANTICANCER AGENT AGAINST GASTRIC CANCER

Sayyada Kazim, Samra Kazim, Sabiha Kazim, Rais A Ansari, Wilfredo Hernandez, Leon Ferder and Dr. Kazim Husain*

ABSTRACT

This study evaluated the anticancer activity of ?-tocotrienol (DT3), a bioactive form of vitamin E, in the inhibition of gastric cancer growth and survival compared with other three forms ?-, ?- and ?-tocotrienol (AT3, BT3 and GT3). DT3 is the most bioactive form of vitamin E in inhibiting the cell proliferation of non-metastatic (AGS) and metastatic (746T) gastric cancer cells followed by GT3 and BT3. However, AT3 is devoid of any inhibitory effect on gastric cancer cell viability. The estimated IC50 values are 80+5, 55+5 and 40+5 ?M for BT3, GT3 and DT3, respectively in both cell lines. DT3 (40 ?M) significantly inhibited malignant transformation (p <0.02, p <0.01), cell migration (p <0.01) and invasion (p < 0.05, p < 0.02) compared to vehicle in AGS and 746T cells. DT3 inhibited markers for epithelial (E-cadherin) to mesenchymal (vimentin) transition (EMT), metastasis (matrix metalloproteinase 9 [MMP9]), angiogenesis (Vascular endothelial growth factor [VEGF]), inflammation (Nuclear factor-kappa B [NF-kB]), and Wnt signaling (?-catenin) and its downstream transcriptional targets C-MYC, Cyclin D1 and survivin compared to vehicle. In addition DT3 also induced apoptosis in gastric cancer cells (AGS and 746T). Taken together, these data demonstrate that DT3 is a potential therapeutic agent in advanced gastric cancer and warrants further investigation for its clinical use in the prevention and treatment of gastric cancer.

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