Brachyantheraoside A₈, a new natural nor-oleanane triterpenoid as a kidney-type glutaminase inhibitor fromStauntonia brachyanthera

Abstract

With the aim of finding a better kidney-type glutaminase (KGA) inhibitor with potential anti-cancer properties, 18 nor-oleanane triterpenoids fromStauntonia brachyanthera, including 2 new ones, were screened against KGA.

Overview of the Development of Glutaminase Inhibitors: Achievements and Future Directions

“…Human hepatoma HepG2 and lung carcinoma A549 cells are found to show high expression levels of GAB and KGA protein . KGA was also found to be highly expressed in SW1990 and erlotinib-resistant NSCLC cells HCC827-ER . Finally, the methods for counting live cells mainly include CellTiter Glo Luminescent Cell Viability Assay kit (Promega) and trypan blue dye exclusion in a hemocytometer.…”

“…Physapubescin and Brachyantheraoside A 8 (Figure ), two novel kidney-type glutaminase (KGA) inhibitors, were identified from natural products by structure-based virtual screening. , The enzyme inhibition experiments indicated that the IC 50 values of physapubescin and brachyantheraoside A 8 were 9.89 and 6.10 μM, respectively, with a closely similar effect compared with BPTES (IC 50 = 8.60 μM). The cell-based assays revealed that the IC 50 value of physapubescin against HCC827-ER and HT1080 cells were 2.73 and 6.99 μM, respectively, and the IC 50 value against the HCC1806 cell was 24.94 μM.…”

Alone and Together: Current Approaches to Targeting Glutaminase Enzymes As Part of Anti-Cancer Therapies

“…caused the enzyme to reduce aggregation), C9 did not exhibit such an effect. Natural-product inhibitors have also been identified, including physapubescin [ 73 ] and brachyantheraoside A8 [ 79 ]. Interestingly, physapubescin shares structural similarity with the benzophenathridinone class of inhibitors, displaying even lower IC 50 .…”

Phytocompounds Targeting Metabolic Reprogramming in Cancer: An Assessment of Role, Mechanisms, Pathways, and Therapeutic Relevance

“…Resveratrol, in combination with cisplatin, shows synergistic effects on decreasing glutamine uptake by downregulating ASCT2 in human hepatoma cells . After glutamine enters the cells, it is first converted to glutamate by glutaminase (GLS), thus glutaminase is considered to be a “gate-keeper” enzyme of glutaminolysis. , The GLS1 isozyme (kidney-type glutaminase) is a downstream target of Myc and a highly upregulated isoform of GLS in many cancers with poor prognosis. ,, Brachyantheraoside A8 blocks glutamine metabolism by inhibiting the enzymatic activity of GLS1 in breast cancer . Physapubescin k allosterically inhibits GLS1 activity in non-small cell lung cancer (NSCLC) and human fibrosarcoma cells .…”