Antiproliferative and Apoptosis-Inducing Effects of Lipophilic Vitamins on Human Melanoma A375 Cells in Vitro

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  • Ishibashi Mai
    Department of Clinical Pharmacology, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences
  • Arai Mariko
    Department of Pharmacy, Kitasato University East Hospital
  • Tanaka Sachiko
    Department of Clinical Pharmacology, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences
  • Onda Kenji
    Department of Clinical Pharmacology, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences
  • Hirano Toshihiko
    Department of Clinical Pharmacology, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences

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The effects of six lipophilic vitamins: tretinoin (ATRA), vitamin D3 (VD3), VE, VK1, VK3, and VK5 on cell proliferation and apoptosis in human A375 melanoma cells were investigated. VD3, VK3, and VK5 were found to inhibit cell proliferation significantly at concentration ranges of 10—100 μmol/L (p<0.01), while the other vitamins did not show inhibitory effects at 100 μmol/L. VK3 and VK5 showed the strongest effects with IC50 values of less than 10 μmol/L. Dacarbazine slightly inhibited the proliferation of A375 cells at a concentration range of 25—100 μmol/L, but the effects were not statistically significant. VK3 and VK5 increased annexin-V positive apoptotic cells, as well as activating caspase-3, in A375 cells. Our findings showed that VD3, VK3, and VK5 inhibited the growth of dacarbazine resistant human melanoma cells, while ATRA, VE, and VK1 had little effect on the cell growth. The effects of VK3 and VK5 were observed at concentrations lower than 10 μmol/L, which are suggested to have resulted from apoptosis-induction in the melanoma cells.

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