Natural Vitamin E isoforms, gamma and delta modulate TGF beta in PC-3 prostate cancer cells.

A107

In early stages of cancer, TGFβ (primarily TGFβ1) inhibits tumor development, but at later stages of tumor progression, cancer cells evade the growth inhibition by TGFβ. TGFβ is switched from a tumor suppressor to a tumor promoter. Lu et al. has demonstrated that the PC-3 cancer cell line exhibits constitutive expression of NF-κB, an anti-apoptotic transcription factor. The constitutive expression of NF-κB conveys resistance to Tumor Necrosis Factor alpha (TNF-α), a natural apoptotic stimuli. Transforming Growth Factor β2 (TGFβ2) has been identified as a factor mediating the constitutive activation of NF-κB. The Alpha-Tocopherol, Beta Carotene study found that substantially fewer participants taking alpha-tocopherol developed prostate cancer. Helzlsouer et al. furthered these findings by showing that high plasma concentrations of gamma-tocopherol enhanced the effects previously seen with alpha-tocopherol. Further research has shown that vitamin E is able to induce cell death in PC-3 cells with the effect being greatly increased when cells are treated with both TNFα and vitamin E, suggesting a possible mechanism of action for TGFβ induced cell death. In this study, the gamma and delta isoforms of vitamin E were tested for their ability to halt cell proliferation in PC-3 prostate cancer cell lines in comparison with alpha-tocopherol at 20, 40 and 60 μM. By western blotting and ELISA assays it was found that the gamma and delta isoforms are more potent inhibitors of cell proliferation than alpha-tocopherol. These natural vitamin E isoforms are able to allow PC-3 cells to overcome the resistance to TNFα-mediated cell death. We further demonstrate that these isoforms down regulate the expression of TGFβ2, NF-κB, and TGFβ Receptor 1.