Antiproliferative and apoptosis-inducing effects of lipophilic vitamins on human melanoma A375 cells in vitro.
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.
Department of Clinical Pharmacology, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Tokyo, Japan.
Mai
M
Ishibashi
Mariko
M
Arai
Sachiko
S
Tanaka
Kenji
K
Onda
Toshihiko
T
Hirano
D017304:Annexin A5 / Q000378:metabolism; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002762:Cholecalciferol / Q000494:pharmacology / Q000627:therapeutic use*; D003606:Dacarbazine / Q000494:pharmacology / Q000627:therapeutic use; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D020128:Inhibitory Concentration 50; D008545:Melanoma / Q000188:drug therapy* / Q000378:metabolism; D014212:Tretinoin / Q000494:pharmacology / Q000627:therapeutic use*; D014812:Vitamin K / Q000494:pharmacology / Q000627:therapeutic use*; D014815:Vitamins / Q000494:pharmacology / Q000627:therapeutic use
D017304:Annexin A5; D000970:Antineoplastic Agents; D014815:Vitamins; D014812:Vitamin K; D002762:Cholecalciferol; D014212:Tretinoin; D003606:Dacarbazine; D053148:Caspase 3