Shahar Orr, Pereman Idan, Khamisie Hazem, Ezov Nirit, Danay Ofer, Khattib Ali, Schweitzer Ron, Khatib Soliman, Mahajna Jamal
Department of Nutrition and Natural Products, Migal - Galilee Research Institute, Kiryat Shmona, Israel.
Department of Biotechnology, Tel Hai College, Kiryat Shmona, Israel.
Heliyon. 2023 Feb 16;9(3):e13756. doi: 10.1016/j.heliyon.2023.e13756. eCollection 2023 Mar.
Tropomyosin receptor kinase B (TrkB) serves as a pivotal factor in various cancers. To identify novel natural compounds with TrkB-inhibiting properties, a screening approach was applied using extracts from a collection of wild and cultivated mushroom fruiting bodies, and Ba/F3 cells that ectopically express TrkB (TPR-TrkB). We selected mushroom extracts that selectively inhibited proliferation of the TPR-TrkB cells. We then evaluated the ability of exogenous interleukin 3 to rescue growth inhibition by the selected TrkB-positive extracts. An ethyl acetate extract of actively inhibited auto-phosphorylation of TrkB. LC-MS/MS analysis of this extract revealed substances that might be responsible for the observed activity. This screening approach demonstrates, for the first time, that extracts originating from the mushroom exhibit TrkB-inhibition properties that might hold therapeutic potential for TrkB-positive cancers.
原肌球蛋白受体激酶B（TrkB）在多种癌症中起着关键作用。为了鉴定具有TrkB抑制特性的新型天然化合物，我们采用了一种筛选方法，使用从野生和栽培蘑菇子实体以及异位表达TrkB（TPR-TrkB）的Ba/F3细胞中提取的提取物。我们选择了能选择性抑制TPR-TrkB细胞增殖的蘑菇提取物。然后，我们评估了外源性白细胞介素3挽救所选TrkB阳性提取物对生长抑制的能力。一种蘑菇的乙酸乙酯提取物能有效抑制TrkB的自磷酸化。对该提取物的液相色谱-串联质谱分析揭示了可能导致观察到的活性的物质。这种筛选方法首次证明，源自该蘑菇的提取物具有TrkB抑制特性，这可能对TrkB阳性癌症具有治疗潜力。
