alpha-Tocopheryl succinate promotes selective cell death induced by vitamin K3 in combination with ascorbate

0349345 - BTÚ 2011 RIV GB eng J - Článek v odborném periodiku
Tomasetti, M. - Strafella, E. - Staffolani, S. - Santarelli, L. - Neužil, Jiří - Guerrieri, R.
alpha-Tocopheryl succinate promotes selective cell death induced by vitamin K3 in combination with ascorbate.
British Journal of Cancer. Roč. 102, č. 8 (2010), s. 1224-1234. ISSN 0007-0920. E-ISSN 1532-1827
Výzkumný záměr: CEZ:AV0Z50520701
Klíčová slova: Vitamins * prostate cancer * cell-death
Kód oboru RIV: ED - Fyziologie
Impakt faktor: 4.831, rok: 2010

A strategy to reduce the secondary effects of anti-cancer agents is to potentiate the therapeutic effect by their combination. A combination of vitamin K3 (VK3) and ascorbic acid (AA) exhibited an anti-cancer synergistic effect. The redox-silent vitamin E analogue alpha-tocopheryl succinate (alpha-TOS) was used in combination with VK3 and AA to evaluate their effect on prostate cancer cells. These cells were sensitive to alpha-TOS and VK3 treatment, but resistant to AA upto 3.2 mM. When combined, a synergistic effect was found for VK3-AA, whereas alpha-TOS-VK3 and alpha-TOS-AA combination showed an antagonist and additive effect, respectively. However, sub-lethal doses of AA-VK3 combination combined with a sub-toxic dose of alpha-TOS showed to induce cell death resembling autoschizis. Associated with this cell demise, lipid peroxidation, DNA damage, cytoskeleton alteration, lysosomal-mitochondrial perturbation, and release of cytochrome c without caspase activation were observed
Trvalý link: http://hdl.handle.net/11104/0189611