L-Lysine α-Oxidase: Enzyme with Anticancer Properties

Abstract

L-lysine α-oxidase (LO), one of L-amino acid oxidases, deaminates L-lysine with the yield of H2O2, ammonia, and α-keto-ε-aminocaproate. Multiple in vitro and in vivo studies have reported cytotoxic, antitumor, antimetastatic, and antitumor activity of LO. Unlike asparaginase, LO has a dual mechanism of action: depletion of L-lysine and formation of H2O2, both targeting tumor growth. Prominent results were obtained on murine and human tumor models, including human colon cancer xenografts HCT 116, LS174T, and T47D with maximum T/C 12, 37, and 36%, respectively. The data obtained from human cancer xenografts in immunodeficient mice confirm the potential of LO as an agent for colon cancer treatment. In this review, we discuss recently discovered molecular mechanisms of biological action and the potential of LO as anticancer enzyme.

Monoclonal Antibody Functionalized, and L-lysine α-Oxidase Loaded PEGylated-Chitosan Nanoparticle for HER2/Neu Targeted Breast Cancer Therapy

“…Nanomedicines are favorable to intravenous injection for the efficient delivery of drugs without any toxicity to normal cells [ 47 ]. In addition, the enzyme LO is known to cause the toxicity of L-lysine in blood plasma [ 3 ]. To verify the blood toxicity of LO, a hemolysis assay was performed and compared the activity of CS-LO-PEG HER NPs and CS-LO PEG NPs.…”

“…L-lysine α-oxidase (LO) was first discovered in Trichoderma viride , then in T. harzianum Rifai, in the 1980s [ 1 , 2 ]. This enzyme has been shown to inhibit the proliferation of cancer cells, such as human lung squamous cell carcinoma (RERF-LC-AI), prostate cancer (PC3), cervical cancer cell line (HeLa), ovarian cancer (SKOV3), breast cancer (MCF7), colon cancers (LS174T and HT29) and erythromyeloblastoid leukemia (K562), without causing any significant damage to normal human umbilical vein endothelial cells (HUVECs) [ 3 , 4 ]. Breast and ovarian cancer cells are more sensitive to LO than others [ 5 ].…”

“…Therefore, deprivation of L-lysine is an important issue caused by LO administration to animals. Although LO is efficient in antitumor activity, an administration of 150 U/kg at a 48 h interval might cause toxicity, weight loss (>30%) and loss of L-lysine in blood plasma, which results in the death of mice [ 3 ]. The LO administration (75 U/Kg of four doses for 10 days at 2 days interval) suppresses the growth of cancer cells in Balb/c nude mice that were transplanted with cancer cells [ 5 ].…”

Inhibition of Glutamine Uptake Resensitizes Paclitaxel Resistance in SKOV3-TR Ovarian Cancer Cell via mTORC1/S6K Signaling Pathway

“…Similar to the experimental results of SKOV3-TR, it was confirmed that cell viability was significantly inhibited in the arginine-, glutamine-, and lysine-deprived culture conditions in SKOV3 cells (data not shown), showing the potential of targeting amino acid metabolism to suppress survival in ovarian cancer, independent of paclitaxel resistance. Previous studies revealed that arginine deprivation induced cell cytotoxicity via the autophagy pathway in ovarian cancer cells [ 41 ], and that lysine deprivation enhanced the anticancer effect through L-lysine α-oxidase-induced oxidative stress [ 54 ]. Although glutamine deprivation-induced cytotoxicity has been reported, little is known about the effects of glutamine deprivation on paclitaxel resistance in ovarian cancer.…”

Anti-Colon Cancer Activity of Dietary Phytochemical Soyasaponin I and the Induction of Metabolic Shifts in HCT116

“…With a very special demand for nutrition, cancer cells increased multiple metabolic processes and overconsumed nutrients in order to meet the energy and biosynthesis required for growth [ 21 ]. In past studies, it had been found that the consumption of certain amino acids, such as asparagine, arginine, and methionine, could be applied to treat amino acid-dependent cancers [ 22 ]. In addition, the degradation of lysine could also inhibit the growth of various cancer cells [ 23 ].…”