Date of Award
Bachelor of Science
Vitamin K serves as a cofactor in the post-translational carboxylation of glutamate to γ-carboxyglutamate (GLA) by the enzyme gamma-glutamyl carboxylase (GGCX). Vitamin K epoxide reductases (VKOR) then oxidize the vitamin K to regenerate the compound’s reduced form. While most of the known γcarboxylated proteins function in coagulation and bone homeostasis, the presence of GGCX and VKOR in a wide variety of tissues suggests that the vitamin and its pathway has more extensive physiological roles. Our previous research has assessed the expression of the vitamin K pathway in triple negative breast cancer cells (TNBCs) and compared the effects of vitamin K1 to those of vitamin K2. These data indicated that K1 promoted, while K2 suppressed, TNBC cell growth and aggressive phenotypes. Here, using cell culture techniques, western blotting, cell-based assays, and qPCR, we expanded on this research by assaying for the effects of K1 and K2 on GLA expression, cell density, viability, cycle kinetics and the expression of the oncogenes cyclin D1 and c-Myc in the TNBC cell line SUM159PT. Our data demonstrated that short term (24h) treatment with K1 did not alter GLA modified protein expression in SUM159PT cells. Despite lack of evidence for γ-carboxylation, K1 exerted biphasic effects on the density of SUM159PT cultures, with minimal impact at low at concentrations and a reduction in density at higher concentration. Neither K1 nor K2 affected cell viability, but the compounds had opposite effects on cell cycle progression. Vitamin K1 tended to reduce the percentage of cells in S and G2/M phases with increasing treatment concentrations, whereas K2 induced dose-dependent entry and accumulation of cells in G2/M coupled with exit from G0/G1. The expected changes in expression of cyclin D1 and c-Myc by 5 μg/mL K1 or K2 treatment were not correlated with the effects of K1 and K2 on cell cycle. In summary, these data highlight novel actions of vitamins K1 and K2 in TNBC cells that may be independent of γ-carboxylation.
Alexander, Monica E., "Investigating the Effects of Vitamin K1 and K2 on the Triple Negative Breast Cancer Cell Line SUM159PT" (2023). Biological Sciences. 96.