Pro-apoptotic properties of vitamin E isomers and novel derivatives in prostate cancer

Current observations in the literature suggest that vitamin E may be a suitable candidate for the adjuvant treatment of cancer and that the eight different isomers comprising vitamin E (α-, β-, γ- and δ- tocopherols and α-, β-, γ- and δ- tocotrienols) are not redundant but functionally unique. To investigate this further, we examined the ability of the following vitamin E isomers and derivatives to inhibit proliferation or to induce cell death in the three prostate carcinogenic cell lines DU145, PC-3 and LNCaP: α-, γ- and δ- tocopherols (α-TOC, γ-TOC and δ-TOC), α-, γ- and δ- tocopherol succinates (α-TOS, γ-TOS and δ-TOS), α-tocopherol glutarate (α-TOG), α-tocopherol maleate (α-TOM), α-tocopherol CEHC metabolite (α-CEHC), β-, γ- and δ- tocotrienols (β-TT, γ-TT and δ-TT), α-, γ- and δ- tocotrienol succinates (α-TS, γ-TS and δ-TS), α-tocopherol polyethylene glycol succinate (TPGS) as well as five synthetic derivatives of the latter (TPGS-a, TPGS-b, TPGS-c, TPGS-d and TPGS-e). Our results suggest that (a) tocotrienols have a greater anti-proliferative potency than tocopherols, (b) γ-TT and δ-TT work synergistically in inducing cell death and are the most effective of all the tocotrienol combinations tested, (c) δ-TS is the most potent of all the tocotrienol succinate analogues tested and more potent than δ-TT, (d) TPGS and its analogues are more effective in inducing cell death than the tocopherols, tocotrienols and their derivatives and (e) TPGS-e is the most effective of all the TPGS analogues tested. The ability of the latter to induce the caspase cascade was confirmed by the partial caspase-dependent cleavage of PARP. Nevertheless, since cell death induced by this compound is insensitive to the inhibition of caspases, further work should be performed to investigate the molecular pathway(s) by which TPGS-e as well as the other TPGS derivatives induce apoptosis in prostate cancer cell lines.

Acknowledgements: This research was partially funded by the Cyprus Research Promotion Foundation (Grant number 0506/06).