Lactic dehydrogenase and cancer an overview

Abstract

Despite the intense scientific efforts made, there are still many tumors that are difficult to treat and the percentage of patient survival in the long-term is still too low. Thus, new approaches to the treatment of cancer are needed. Cancer is a highly heterogeneous and complex disease, whose development requires a reorganization of cell metabolism. Most tumor cells downregulate mitochondrial oxidative phosphorylation and increase the rate of glucose consumption and lactate release, independently of oxygen availability (Warburg effect). This metabolic rewiring is largely believed to favour tumor growth and survival, although the underlying molecular mechanisms are not completely understood. Importantly, the correlation between the aerobic glycolysis and cancer is widely regarded as a useful biochemical basis for the development of novel anticancer strategies. Among the enzymes involved in glycolysis, lactate dehydrogenase (LDH) is emerging as a very attractive target for possible pharmacological approaches in cancer therapy. This review addresses the state of the art and the perspectives concerning LDH both as a useful diagnostic marker and a relevant molecular target in cancer therapy and management.

TRPM7 in CHBP-induced renoprotection upon ischemia reperfusion-related injury

“…In HR TCMK-1 cells, LDH release is a reliable marker of hypoxic injury correlating well with necrotic cell death 40 . HMGB1, an endogenous ligand for TLR4, is a TLR4-dependent inflammatory mediator in renal IR-related injuries 41 .…”

“…Cytotoxicity was measured by lactate dehydrogenase (LDH) assay, which was performed as described 40 . Fifty μl medium on 24-well plates growing cells was taken from each well, the cell supernatants was detect by automatic biochemistry analyzer (Siemens, Berlin, Germany).…”

Monocarboxylate transporter 1 (MCT1), a tool to stratify acute myeloid leukemia (AML) patients and a vehicle to kill cancer cells

“…Metabolic adaptation involves an orchestrated remodelling of metabolic intervenients and in lactate metabolism the most important elements are monocarboxylate transporters (MCTs) [ 9 , 10 ] - in cancer MCT1 and MCT4 seem to be the most relevant [ 11 , 12 , 39 ]; and lactate dehydrogenases (LDH), which are able to convert lactate and pyruvate in both ways and have even been considered as putative therapeutic targets in cancer [ 40 , 41 ]. HL60 reacted to lactate and VEGF by increasing MCT1 levels and THP1 expresses high levels of MCT1, which are maintained upon lactate and VEGF exposure (Figure 3A and 3C ).…”

Lactate dehydrogenase is a prognostic indicator in patients with hepatocellular carcinoma treated by sorafenib: results from the real life practice in HBV endemic area

“…LDH is a key enzyme in the conversion of pyruvate to lactate under anaerobic conditions [9]. The Warburg effect may stimulate the secretion of LDH; and the increased level of LDH may in turn amplify the Warburg effect [25]. Hypoxia in the tumor microenvironment, which may be partially accompanied by the elevated LDH level, is sufficient to activate HIF-dependent expression of several downstream genes [10].…”