Department of Clinical Pharmacology, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Tokyo, Japan.
Biol Pharm Bull. 2012;35(1):10-7. doi: 10.1248/bpb.35.10.
The effects of six lipophilic vitamins: tretinoin (ATRA), vitamin D(3) (VD(3)), VE, VK(1), VK(3), and VK(5) on cell proliferation and apoptosis in human A375 melanoma cells were investigated. VD(3), VK(3), and VK(5) 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. VK(3) and VK(5) showed the strongest effects with IC(50) 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. VK(3) and VK(5) increased annexin-V positive apoptotic cells, as well as activating caspase-3, in A375 cells. Our findings showed that VD(3), VK(3,) and VK(5) inhibited the growth of dacarbazine resistant human melanoma cells, while ATRA, VE, and VK(1) had little effect on the cell growth. The effects of VK(3) and VK(5) were observed at concentrations lower than 10 μmol/L, which are suggested to have resulted from apoptosis-induction in the melanoma cells.
视黄醇（ATRA）、维生素 D（3）（VD（3））、VE、VK（1）、VK（3）和 VK（5）对人 A375 黑素瘤细胞增殖和凋亡的影响。发现 VD（3）、VK（3）和 VK（5）在 10-100μmol/L 的浓度范围内显著抑制细胞增殖（p<0.01），而其他维生素在 100μmol/L 时没有抑制作用。VK（3）和 VK（5）表现出最强的作用，IC（50）值小于 10μmol/L。达卡巴嗪在 25-100μmol/L 的浓度范围内轻微抑制 A375 细胞的增殖，但无统计学意义。VK（3）和 VK（5）增加了 A375 细胞中 Annexin-V 阳性凋亡细胞，并激活了 caspase-3。我们的研究结果表明，VD（3）、VK（3）和 VK（5）抑制了达卡巴嗪耐药的人黑素瘤细胞的生长，而 ATRA、VE 和 VK（1）对细胞生长几乎没有影响。VK（3）和 VK（5）的作用在浓度低于 10μmol/L 时观察到，这可能是由于黑素瘤细胞的凋亡诱导所致。
