Isoangustone A

Isoangustone A is an anticancer and anti-inflammatory agent. Isoangustone A induces cancer cells apoptosis and autophagic cell death[1][2][3].

Signaling Pathways >> Apoptosis >> Apoptosis

Research Areas >> Cancer

Signaling Pathways >> Autophagy >> Autophagy

Research Areas >> Inflammation/Immunology

Apoptosis, Autophagy[2]

Isoangustone A (10 and 20 μM; 48 and 72 h) 抑制 SK-MEL-28 细胞增殖并诱导 G1 期细胞周期阻滞[1]。 Isoangustone A (10 and 20 μM; 48 h) 通过 Akt/GSK3β 和 MKK4/MKK7/JNKs 信号通路介导 G1 期相关蛋白的丰度降低[1]。 Isoangustone A 通过 ATP 竞争方式直接结合抑制 PI3-K、MKK4 和 MKK7 激酶活性[1]。 Isoangustone A (20 μM; 0.5-4 h) 通过激活 AMPK 信号诱导结直肠癌细胞自噬[2]。 Isoangustone A (1-20 μM; 0-100 min) 抑制线粒体呼吸[2]。 Isoangustone A (15 μM; 6 h) 诱导 SW480 细胞凋亡[2]。 Isoangustone A (1-20 μΜ; 3 days) 抑制人肾系膜细胞的纤维化和炎症[3]。 Cell Proliferation Assay[1] Cell Line: SK-MEL-28 Concentration: 10 and 20 μM Incubation Time: 48 and 72 h Result: Inhibited proliferation in a dose- and time-dependent manner. Cell Cycle Analysis[1] Cell Line: SK-MEL-28 Concentration: 10 and 20 μM Incubation Time: 48 h Result: Caused cell cycle arrest at G1 phase. Western Blot Analysis[1] Cell Line: SK-MEL-28 Concentration: 10 and 20 μM Incubation Time: 48 h Result: Inhibited the expression of cyclin D1 and cyclin E. Suppressed phosphorylation of Rb in a dose-dependent manner. Inhibited the phosphorylation of Akt (Ser473, Thr308) and GSK3β (Ser9). Suppressed the phosphorylation of JNK1/2, but had no effect on ERK1/2 or p38. Cell Autophagy Assay[2] Cell Line: SW480 cells Concentration: 20 μM Incubation Time: 0.5, 2 and 4 h Result: Deformed mitochondria, nondegradable cellular debris were all observable together with autophagic vacuoles in cells after 4 h. Apoptosis Analysis[2] Cell Line: SW480 cells Concentration: 15 μM Incubation Time: 6 h Result: Induced elevation of apoptotic Annexin V+/PI- and Annexin V+/PI+ cell populations.

Isoangustone A (2 or 10 mg/kg; i.p.; daily for 35 days) 显著降低小鼠 SK-MEL-28 异种移植物的肿瘤生长、体积和重量[1]。 Animal Model: Male Balb/c nu/nu mice, SK-MEL-28 xenograft model[1] Dosage: 2 or 10 mg/kg Administration: Intraperitoneal injection, daily for 35 days Result: Significantly suppressed tumor weight compared to the control group. Markedly inhibited the expression of proliferating cell nuclear antigen (PCNA). Decreased phosphorylation levels of Akt.

[1]. Song NR, et al. Isoangustone A, a novel licorice compound, inhibits cell proliferation by targeting PI3K, MKK4, and MKK7 in human melanoma. Cancer Prev Res (Phila). 2013 Dec;6(12):1293-303.  

[2]. Tang S, et al. Isoangustone A induces autophagic cell death in colorectal cancer cells by activating AMPK signaling. Fitoterapia. 2021 Jul;152:104935.  

[3]. Li J, et al. Isoangustone A suppresses mesangial fibrosis and inflammation in human renal mesangial cells. Exp Biol Med (Maywood). 2011 Apr 1;236(4):435-44.