Mevalonate (lithium salt)

Mevalonate is an intermediate in the mevalonate pathway of cholesterol synthesis.¹ It inhibits cell death induced by the HMG-CoA reductase inhibitor simvastatin in C2C12 myoblasts when used at concentrations ranging from 80 to 110 µM.² Mevalonate (500 µM) reverses decreases in proliferation induced by the HMG-CoA reductase inhibitor lovastatin in several colon cancer cell lines, including RKO and SW480 cells.³ It increases lovastatin-induced decreases in the expression of the genes encoding Axin2, ectodermal-neural cortex 1 (ENC1), BCL2-like 1 (BCL2-L1), and cyclin D1 when used at a concentration of 500 µM. Mevalonate (50 µM) increases Rac1 protein levels, as well as increases Rac1 farnesylation induced by the arachidonic metabolite 15(S)-HETE in human dermal microvascular endothelial cells (HDMVECs).⁴

1.Yazawa, H., Zimmermann, B., Asami, Y., et al.Simvastatin promotes cell metabolism, proliferation, and osteoblastic differentiation in human periodontal ligament cellsJ. Periodontol.76(2)295-302(2005) 2.Moschetti, A., Dagda, R.K., and Ryan, R.O.Coenzyme Q nanodisks counteract the effect of statins on C2C12 myotubesNanomedicine37102439(2021) 3.Gong, L., Xiao, Y., Xia, F., et al.The mevalonate coordinates energy input and cell proliferationCell Death Dis.10(4)327(2019) 4.Singh, N.K., Kundumani-Sridharan, V., and Rao, G.N.12/15-Lipoxygenase gene knockout severely impairs ischemia-induced angiogenesis due to lack of Rac1 farnesylationBlood118(20)5701-5712(2011)