Data Sheet 1_Combined vitamins D3 and K2 as potential modulators of multiple myeloma cell pathophysiology: transcriptomic and epigenetic effects under standard culture and bone marrow-like conditions.zip

Under normoxic conditions, 444 DEGs and 5,269 DMPs were identified in U266 cells, whereas 4,575 DEGs and 8,710 DMPs were detected in MM1S cells. These findings demonstrate that the molecular response to the combined vitamin treatment differed between MM cell lines and oxygen conditions, with a particularly restricted transcriptional response in U266 cells and reduced DNA methylation changes under hypoxia. These findings suggest cell line-specific adaptation mechanisms to low oxygen conditions, similar to those occurring in the tumor microenvironment in vivo.

Focusing on the effects of vitamin treatment under hypoxia, we identified several genes, including ABCA1, ADAMTS9, and RUNX1T1, that may contribute to the antitumor mechanisms of VD and VK. Notably, hypermethylation of the MCOLN3 gene correlated with reduced expression, identifying MCOLN3 as a potential target for further investigation into the molecular effects of vitamin D3 and vitamin K2.</p>Discussion<p>Overall, these findings demonstrate that oxygen availability influences the antitumor effects of combined vitamin D3 and vitamin K2 treatment and reveal molecular changes that may contribute to their mechanism of action.

They also highlight the importance of considering physiological oxygen conditions in in vitro studies of multiple myeloma.</p>