L-Type amino acid transporter 1 (LAT1) is overexpressed in malignant tumor cells to support their growth and proliferation. BCH is a LAT1 inhibitor that inhibits the uptake of [14C]L-leucine (1μM) in KB, Saos2, and C6 cells with IC50 values of 75.3±6.7μM, 78.8±3.5μM, and 73.1±4.5μM, respectively. BCH also exhibited anti-proliferative effects on KB, Saos2, and C6 cells with IC50 values of 6.9±0.4mM, 5.6±0.7mM, and 6.5 ± 0.9mM, respectively. Treatment of cancer cells with 20 mM BCH significantly increased the proportion of TUNEL-positive cells in comparison to the untreated groups. BCH treatment also significantly promoted proteolytic cleavage of procaspase-7 and procaspase-3 in cancer cells.[1] Treatment of primary mouse hepatocytes with 10mM BCH led to 38% and 50% increase in cellular and extracellular levels of glutamate, respectively. In normal C57BL/6J mice, treatment with 0.7g/kg BCH for 6 hr significantly increased glutamate level, glutamate dehydrogenase activity, and NAD+/NADH ratio in the liver. In mice fed with high fat/high fructose western diet, peritoneal injection of BCH (0.7g/kg/day) for 8 weeks reduced the level of triglyceride by 30% compared to the control group. BCH treatment also reduced high fat/high fructose diet-induced stress, inflammation and ameliorated hepatic injury and hyperglycemia in mice.[2]
作用机制
BCH is a selective LAT1 inhibitor that can suppress cell growth and induce apoptosis.[1]
BCH 细胞实验
Cell Line
Concentration
Treated Time
Description
References
Human breast adenocarcinoma cells (MCF-7)
100 µM
72 h
Assess apoptosis and cytotoxicity. Results showed that compound 1 significantly reduced the percentage of viable cells and induced apoptosis.
Apoptosis. 2020 Jun;25(5-6):426-440.
Human aortic smooth muscle cells (AoSMC)
1-100 µM
24 h
Assess cell viability and morphological changes. Results showed that at concentrations below 50 µM, compound 1 had minimal effects on AoSMC viability.
Apoptosis. 2020 Jun;25(5-6):426-440.
Human umbilical vein endothelial cells (HUVEC)
1-100 µM
24 h
Assess cell viability and morphological changes. Results showed that at concentrations below 10 µM, compound 1 had minimal effects on HUVEC viability.
Apoptosis. 2020 Jun;25(5-6):426-440.
African green monkey kidney fibroblast-like cells (COS1 cells)
1 mM
Inhibited LAT1 and LAT2 activity
Thyroid. 2022 Sep;32(9):1129-1137.
organotypic forebrain slice culture model
10 mM
24 h
To study the effect of SLC7A5/SLC3A2 inhibition on BCAA transport, results showed BCH had little effect on metabolite abundance
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