Branched-chain amino acids catabolism and cancer progression: focus on therapeutic interventions

Abstract

Branched-chain amino acids (BCAAs), including valine, leucine, and isoleucine, are crucial amino acids with significant implications in tumorigenesis across various human malignancies. Studies have demonstrated that altered BCAA metabolism can influence tumor growth and progression. Increased levels of BCAAs have been associated with tumor growth inhibition, indicating their potential as anti-cancer agents. Conversely, a deficiency in BCAAs can promote tumor metastasis to different organs due to the disruptive effects of high BCAA concentrations on tumor cell migration and invasion. This disruption is associated with tumor cell adhesion, angiogenesis, metastasis, and invasion. Furthermore, BCAAs serve as nitrogen donors, contributing to synthesizing macromolecules such as proteins and nucleotides crucial for cancer cell growth. Consequently, BCAAs exhibit a dual role in cancer, and their effects on tumor growth or inhibition are contingent upon various conditions and concentrations. This review discusses these contrasting findings, providing valuable insights into BCAA-related therapeutic interventions and ultimately contributing to a better understanding of their potential role in cancer treatment.

Application of the HILIC-MS Novel Protocol to Study the Metabolic Heterogeneity of Glioblastoma Cells

“…In metabolomics studies, it is becoming a tool for the quantification of polar or ionic molecules in biological samples, characterization of metabolic nuances and for the identification of putative biomarkers and drug metabolites. We tested around 150 polar and ionic compounds of interest (Table 2) and evaluated the possibility of their separation on polar columns and subsequent detection and quantification by MS. Based on the previously published results that revealed the capability of glioblastoma cells to readily dispose from culture media glucose and branched-chain amino acids [3,5,[9][10][11][12][13][14]17], we focused on possibility to separate, detect and quantify amino acids in biological matrices by LC-MS. Since leucine and isoleucine are constitutive isomers with identical m/z, we selected for LC separation cHILIC column [10], which is capable to sufficiently separate these two amino acids.…”

“…The limitations in supplementation of glioblastoma cells with glucose in situ, together with assumption that transformed metabolism of glioblastoma cells can also engage other substrates, including amino acids [3,[9][10][11][12][13], are bases for postulating the question about metabolic heterogeneity of glioblastoma cells regarding substrates other than glucose. Indeed, our results confirm that glioblastoma cells remove some of amino acids from their milieu.…”

“…Examples of these alterations include changes in glucose and amino acid metabolism. Glioblastoma cells have been shown to rely on glucose and several amino acids to support their high energy demands [9][10][11][12][13][14], as well as to utilize their carbon skeletons for anabolic processes such as lipid [15,16] and nucleotide synthesis [17]. Despite the genetic and cellular heterogeneity observed in glioblastoma cells within tumor [4], as well as heterogeneity in their metabolism [18][19][20], targeting metabolic pathways has emerged as a promising therapeutic strategy.…”

Application of the Hydrophilic Interaction Liquid Chromatography (HILIC-MS) Novel Protocol to Study the Metabolic Heterogeneity of Glioblastoma Cells

“…In metabolomics studies, it is becoming a tool for the quantification of polar or ionic molecules in biological samples, characterization of metabolic nuances and for the identification of putative biomarkers and drug metabolites. We tested around 150 polar and ionic compounds of interest ( Table 2 ) and evaluated the possibility of their separation on polar columns and subsequent detection and quantification by MS. Based on the previously published results that revealed the capability of glioblastoma cells to readily dispose from culture media glucose and branched-chain amino acids [ 3 , 5 , 9 , 10 , 11 , 12 , 13 , 14 , 17 ], we focused on the possibility to separate, detect and quantify amino acids in biological matrices by LC-MS. Since leucine and isoleucine are constitutive isomers with identical m / z , we selected for LC the separation cHILIC column [ 10 ], which is capable of sufficiently separating these two amino acids.…”

“…Examples of these alterations include changes in glucose and amino acid metabolism. Glioblastoma cells have been shown to rely on glucose and several amino acids to support their high energy demands [ 9 , 10 , 11 , 12 , 13 , 14 ], as well as to utilize their carbon skeletons for anabolic processes such as lipid [ 15 , 16 ] and nucleotide synthesis [ 17 ]. Despite the genetic and cellular heterogeneity observed in glioblastoma cells within tumors [ 4 ], as well as heterogeneity in their metabolism [ 18 , 19 , 20 ], targeting metabolic pathways has emerged as a promising therapeutic strategy.…”