Andrographolide induces apoptosis via down-regulation of glyoxalase 1 and HMG-CoA reductase in HL-60 cells

Abstract

Andrographolide (Andro) is the major active component of the traditional herbal bitter tea Andrographis paniculata. We tested the hypothesis that Andro exerted its antitumor activities through its effects on three key survival enzymes, glyoxalase 1 (GLO1), glutamate-cysteine ligase catalytic subunit (GCLC) and HMG-CoA reductase (HMGCR), leading to cancer cell apoptosis. In human leukemia HL-60 cells Andro could reduce cholesterol levels, accompanied with down-regulation of Ras translocation to the membrane and downstream phosphorylation of Akt and ERK. Based on results obtained using specific inhibitors, LY294002 (PI3K inhibitor), U0126 (MEK1/2 inhibitor), and JSH-23 (NF-κB activation inhibitor), we proposed that the apoptotic effects of Andro in HL-60 cells arose because of interactions with the Ras/Akt/NF-κB/GLO1 and Ras/Raf/ERK/NF-κB/GLO1 pathways. Andro has a potential to be used as a functional food ingredient to prevent and manage inflammatory diseases including cancers.

Keywords

• Andrographolide
• Glyoxalase 1
• Glutamate-cysteine ligase catalytic subunit
• HMG-CoA reductase
• Apoptosis