Syrosingopine

Syrosingopine treatment leads to high intracellular lactate levels and thereby end-product inhibition of lactate dehydrogenase by inhibiting the Lactate Transporters MCT1 and MCT4. The loss of NAD+ regeneration capacity due to combined metformin and syrosingopine treatment results in glycolytic blockade, leading to ATP depletion and cell death. ^{<a class="sref" href="#s_ref">[1]</a>}

HCT116 cells are grown to 80% confluency in DMEM and pre-treated with compounds (10 μM) for 2 hours. After ishing with PBS, cytosolic depletion is performed by scraping cells and incubating with 1.9ml digitonin buffer for 30 minutes on ice.And then used for DARTS assay. For ATP and lactate measurement,HeLa and HAP1 are seeded at 15000 cells/well or 30000 cells/well. After Syrosingopine incubation, cells are ished with PBS and lysed with 22.5 μL HCl. Cell lysates are neutralized with 7.5 μL 1M Tris-base and incubated with 30 μL detection reagent. Luminescence is recorded after 1 hour and intracellular lactate concentrations determined from a standard curve.

Syrosingopine treatment leads to reduced serum lactate levels significantlyn, and higher intracellular lactate from liver tumor nodules in syrosingopine-treated liver tumor model mice. ^{<a class="sref" href="#s_ref">[1]</a>}