Lovastatin (Mevinolin, MK-803)

Lovastatin inhibits LPS- and cytokine-mediated production of NO and expression of iNOS in rat primary astrocytes. This compound inhibits LPS-induced expression of TNF-alpha, IL-1beta, and IL-6 in rat primary astrocytes, microglia, and macrophages. [1]

This chemical results in over 95% inhibition of DNA synthesis as measured by incorporation of [3H]thymidine into DNA. It synchronizes cells in the G1 and not in the G0 phase of the cell cycle. It has a similar growth-inhibitory activity against ras-dependent as well as ras-independent cell lines. [2]

This agent produces a profound reduction of apolipoprotein-B-containing lipoproteins, especially LDL cholesterol and, to a lesser extent, plasma triglyc- erides, and a small increase in HDL cholesterol. [3]

It arrests cells by inhibiting the proteasome, which results in the accumulation of p21 and p27, leading to G1 arrest. This compound is an inhibitor of hydroxymethyl glutaryl (HMG)-CoA reductase, the rate-limiting enzyme in cholesterol synthesis. It can be used to arrest cultured cells in the G1 phase of the cell cycle, resulting in the stabilization of the cyclin-dependent kinase inhibitors (CKIs) p21 and p27. [4]

This chemical (2-10 mM) arrests cells in G1 and also prolonged--or arrested a minor fraction of cells in--the G2 phase of the cell cycle in human bladder carcinoma T24 cell line expressing activated p21ras. It (50 mM) is cytotoxic in human bladder carcinoma T24 cell line expressing activated p21ras. [5]

• Líneas celulares

  Astrocytes

• Concentraciones

  10 μM

• Tiempo de incubación

  8 h

• Método

  Cells preincubated in serum-free media with 10 µM lovastatin or 5 mM NaPA, or a combination of 2 µM this compound and 2 mM NaPA for 8 h received 1 µg/ml of LPS.

• Modelos animales

  Male BALB/c athymic mice

• Dosificaciones

  100 mg/kg

• Administración

  o.g.