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- W2789127456 abstract "3826 Background: Pancreatic cancer is one of the most lethal cancers in need of novel interventions. A role for dietary bioactive compounds in pancreatic cancer prevention is plausible because epidemiological studies indicate that consumption of fruits, vegetables, and cereal foods is associated with a lower risk of developing pancreatic cancer. Tocotrienols are bioactive components of cereal foods such as oats, barley, rice bran, and palm. These compounds have been demonstrated to have anticancer and chemopreventive activity in a wide variety of cancer types; however their activity in pancreatic cancer is unknown. In this study we investigated the comparative effects of the four natural tocotrienol compounds in order to determine the most bioactive tocotrienol against pancreatic cancer Methods: We first determined the anti-proliferative (MTT assay) and pro-apoptotic activity of α, β, γ and δ-tocotrienol in immortalized normal human pancreatic ductal epithelial cells (HPDE C7), HPDE cells transformed with oncogenic Kras (C7-Kras), as well as human pancreatic cancer cell lines MiaPaCa-2 and AsPc-1. We then determined the effect of the tocotrienol compounds on malignant transformation (colony formation) in MiaPaca-2 cells and NF-κB/p65 activity in these cells. The activity of the tocotrienol was also compared to gemcitabine, α-tocopherol, and δ-tocopherol. Results: Tocotrienols significantly inhibited the cell growth of transformed C7-Kras, and pancreatic cancer cells in a concentration and time-dependent manner but had no effect on ‘normal’ HPDE cells. The IC 50 of growth inhibition were 40, 45 and 60 μ M for δ, γ and β tocotrienol compounds, respectively. The IC 50 of growth inhibition for gemcitabine was 20 μ M. In contrast α-tocotrienol, α-tocopherol and δ-tocopherol had no growth inhibitory activity. Malignant transformation was inhibited by 70, 30, 19 and 6% with δ, γ, β and α tocotrienol compounds, respectively in MiaPaca-2 cells. Malignant transformation inhibition for gemcitabine was 89%.The apoptosis inducing activity of δ tocotrienol was far greater than γ and β-tocotrienols and gemcitabine. Furthermore nuclear DNA binding of NF-κB/p65 activity was inhibited by 36, 30, 15 and 5% with δ, γ, β and α tocotrienols, respectively. Conclusion: (1) δ-tocotrienol is the most bioactive tocotrienol compound against pancreatic cancer; (2) δ-tocotrienol is not toxic to non-transformed pancreatic epithelial cells; (3) δ-tocotrienol has more apoptotic activity against pancreatic cancer cells compared to gemcitabine; (4) δ and γ-tocotrienols significantly inhibit nuclear DNA binding activity of NF-κB/p65. These data support further studies to determine the role of δ-tocotrienol in the prevention of pancreatic cancer progression." @default.
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- W2789127456 date "2008-05-01" @default.
- W2789127456 modified "2023-09-24" @default.
- W2789127456 title "Delta-tocotrienol is the most bioactive natural tocotrienol in the prevention of pancreatic cancer transformation" @default.
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