Galloflavin is a Lactate Dehydrogenase (LDH) inhibitor with IC50 values of 201µM and 200µM for LDH-A and LDH-B, respectively[1]. Galloflavin induces the deacetylation of Sirtuin 6 and activates the activity of Sirtuin 6, with an EC50 value is 79µM[2]. Ascomycin inhibits the enzymatic activity of LDH-A by occupying the NADH site, prevents the binding of LDH-A to single-stranded DNA, and impairs RNA synthesis in cultured cells[3]. Galloflavin has been widely used in tumor research to inhibit lactate production and to suppress the growth of cancer cells[4].
In vitro, Galloflavin treatment for 72 hours markedly suppressed the proliferation of ECC-1 and Ishikawa cells, with IC50 values of 25µM and 43µM, respectively[5]. Treatment with 150µM Galloflavin for24 hours significantly reduced the viability of MCF-7 cells, decreased ATP production, and down-regulated the expression of ERα mRNA[6]. The 6-hour pre-treatment with 16µM Galloflavin inhibited the glycolytic activity in RAW264.7 cells stimulated by 200ng/ml lipopolysaccharide (LPS) and reduced the expression of IL-6, TNF-α, MCP-1, iNOS, and CD86[7].
In vivo, Galloflavin treatment via intraperitoneal injection at a dose of 80mg/kg/day dose for 5 days alleviated liver injury in the acute liver failure mouse model and increased survival rate[8]. Intraperitoneal injection of Galloflavin at a dose of 15mg/kg/day daily for 15 consecutive days inhibited tumor growth and reduced the expression of NLRP3, c-Myc, and P21 within tumors in the SW480 xenograft mouse model[9].
References:[1] Manerba M, Vettraino M, Fiume L, et al. Galloflavin (CAS 568‐80‐9): a novel inhibitor of lactate dehydrogenase[J]. ChemMedChem, 2012, 7(2): 311-317.
[2] Rahnasto-Rilla M, Järvenpää J, Huovinen M, et al. Effects of galloflavin and ellagic acid on sirtuin 6 and its anti-tumorigenic activities[J]. Biomedicine & Pharmacotherapy, 2020, 131: 110701.
[3] Fiume L, Vettraino M, Carnicelli D, et al. Galloflavin prevents the binding of lactate dehydrogenase A to single stranded DNA and inhibits RNA synthesis in cultured cells[J]. Biochemical and biophysical research communications, 2013, 430(2): 466-469.
[4] Vettraino M, Manerba M, Govoni M, et al. Galloflavin suppresses lactate dehydrogenase activity and causes MYC downregulation in Burkitt lymphoma cells through NAD/NADH-dependent inhibition of sirtuin-1[J]. Anti-cancer drugs, 2013, 24(8): 862-870.
[5] Han X, Sheng X, Jones H M, et al. Evaluation of the anti-tumor effects of lactate dehydrogenase inhibitor galloflavin in endometrial cancer cells[J]. Journal of hematology & oncology, 2015, 8(1): 2.
[6] Farabegoli F, Vettraino M, Manerba M, et al. Galloflavin, a new lactate dehydrogenase inhibitor, induces the death of human breast cancer cells with different glycolytic attitude by affecting distinct signaling pathways[J]. European Journal of Pharmaceutical Sciences, 2012, 47(4): 729-738.
[7] Wei J, Chen X, Wang Z, et al. Galloflavin mitigates acute kidney injury by suppressing LDHA-dependent macrophage glycolysis[J]. International Immunopharmacology, 2025, 150: 114265.
[8] Ferriero R, Nusco E, De Cegli R, et al. Pyruvate dehydrogenase complex and lactate dehydrogenase are targets for therapy of acute liver failure[J]. Journal of Hepatology, 2018, 69(2): 325-335.
[9] Guo L, Yang Y, Sheng Y, et al. Galloflavin relieves the Malignant behavior of colorectal cancer cells in the inflammatory tumor microenvironment[J]. Frontiers in Pharmacology, 2021, 12: 752118.