Gboxin is an inhibitor of oxidative phosphorylation (OXPHOS) in cancer cells and can be targeted to inhibit glioblastoma (GBM)[1]. Gboxin is a trisubstituted benzimidazolium compound containing a positive charge that can specifically inhibit the growth of multiple cancer cell lines[2]. Gboxin specifically inhibits GBM growth by inhibiting the activity of F0F1 ATPase complex V, but its anti-GBM effect is severely limited by poor blood circulation, blood-brain barrier (BBB) and non-specific GBM tissue/cell uptake[3]. Gboxin can inhibit the expression of thioredoxin-interacting protein, which is a regulator of glucose uptake and consumption and a target of oxidative phosphorylation OXPHOS[4].
In vitro, Gboxin (0-15μM) treatment of HTS cells, primary MEF cells and astrocytes for 96h significantly inhibited the growth of HTS cells, but did not inhibit the growth of primary MEFs and astrocytes, and reduced the mitochondrial membrane potential in HTS cells[5].
References:
[1] Zou Y, Sun Y, Wang Y, et al. Cancer cell-mitochondria hybrid membrane coated Gboxin loaded nanomedicines for glioblastoma treatment[J]. Nature Communications, 2023, 14(1): 4557.
[2] Yao S, Yin J, Liu W, et al. A novel Gboxin analog induces OXPHOS inhibition and mitochondrial dysfunction-mediated apoptosis in diffuse large B-cell lymphoma[J]. Bioorganic Chemistry, 2022, 127: 106019.
[3] Jiao X, Yu X, Gong C, et al. Erythrocyte-cancer hybrid membrane-camouflaged mesoporous silica nanoparticles loaded with gboxin for glioma-targeting therapy[J]. Current Pharmaceutical Biotechnology, 2022, 23(6): 835-846.
[4] Crunkhorn S. Targeting cancer cell metabolism in glioblastoma[J]. Nature Reviews Cancer, 2019, 19(5): 250-250.
[5] Shi Y, Lim S K, Liang Q, et al. Gboxin is an oxidative phosphorylation inhibitor that targets glioblastoma[J]. Nature, 2019, 567(7748): 341-346.
Gboxin是癌细胞中氧化磷酸化（OXPHOS）的抑制剂，能够靶向抑制胶质母细胞瘤（GBM）[1]。Gboxin是一种含有正电荷的三取代苯并咪唑鎓化合物，可特异性抑制多种癌细胞系的生长[2]。Gboxin通过抑制F0F1 ATP酶复合物V的活性来特异性抑制GBM生长，然而其抗GBM作用受到血液循环不良、血脑屏障（BBB）和非特异性GBM组织/细胞摄取的严重限制[3]。Gboxin能够抑制硫氧还蛋白相互作用蛋白的表达，硫氧还蛋白相互作用蛋白是葡萄糖摄取和消耗的调节剂，也是氧化磷酸化OXPHOS的靶标[4]。
在体外，Gboxin（0-15μM）处理HTS细胞、原代MEF细胞和星形胶质细胞96h，显著抑制了HTS细胞的生长，但不抑制原代MEF和星形胶质细胞的生长，降低了HTS细胞中线粒体膜电位[5]。