CUR5g

CUR5g is a potent Autophagy inhibitor. CUR5g selectively inhibits autophagosome degradation in cancer cells by blocking autophagosome-lysosome fusion. CUR5g blocks the recruitment of STX17 to autophagosomes via a UVRAG-dependent mechanism, resulting in the inability of autophagosomes to fuse with lysosomes. CUR5g improves the anticancer effect of Cisplatin (HY-17394) against A549 cells both in vitro and in vivo[1].

Research Areas >> Cancer

Signaling Pathways >> Autophagy >> Autophagy

CUR5g (0-40 μM, 0-24 h) 选择性诱导癌细胞自噬体积累[1]。 CUR5g（0-40 μM，0-24 小时）上调 LC3B-II 和 sequestosome 1 (SQSTM1) 水平[1]。 CUR5g (0-40 μM, 24 h) 抑制 A549 细胞增殖和迁移，但不诱导细胞凋亡或坏死[1]。 Cell Autophagy Assay[1] Cell Line: A549 cells Concentration: 0, 1, 5, 10, 20, and 40 μM Incubation Time: 3, 6, 12, and 24 h Result: Induced extensive cytoplasmic vacuolization, and GFP-LC3B signal shifted from diffuse cytosolic staining to a punctate pattern outlining autophagosomes. Western Blot Analysis[1] Cell Line: A549 cells Concentration: 0, 1, 5, 10, 20, and 40 μM Incubation Time: 0, 1, 3, 6, 12, and 24 h Result: Up-regulated LC3B-II and sequestosome 1 (SQSTM1) levels time- and dose-dependently. This increase was not the result of enhanced transcription, as mRNA expression of SQSTM1 and LC3B were not increased within CUR5g-exposed cells, suggesting that CUR5g might block autophagic flux rather than increase autophagosome formation. Cell Proliferation Assay[1] Cell Line: A549 cells Concentration: 0, 1, 5, 10, 20, and 40 μM Incubation Time: 24 h Result: Exhibited great toxicity to A549 cells at 20 μM. Slightly decreased A549 cell number at 10 µM, while decreased the number of A549 cells significantly at 20 µM. Showed no discernable activity in healthy human umbilical vein endothelial cell (HUVEC) viability at 40 µM.

CUR5g (40 mg/kg，尾静脉注射，每 2 天一次，15 天) 与顺铂(Cisplatin，HY-17394) (1 mg/kg) 具有协同抗癌作用，并抑制体内自噬通量[1]。 Animal Model: BALB/c nude mice (4-week-old, A549 cells were subcutaneously injected into the right scapula of each nude mouse)[1] Dosage: 40 mg/kg, CUR5g (40 mg/kg) and Cisplatin (1 mg/kg) Administration: Injected via caudal vein, once every 2 days for up to 15 days Result: Retarded the growth of xenografted tumors, whereas the combination treatment with Cisplatin almost completely inhibited tumor growth. Promoted the cisplatin sensitivity of A549 cells by inhibiting autophagic flux.

[1]. Chen J, et al. CUR5g, a novel autophagy inhibitor, exhibits potent synergistic anticancer effects with cisplatin against non-small-cell lung cancer. Cell Death Discov. 2022 Oct 31;8(1):435.