β,β-Dimethylacrylshikonin

β,β-Dimethylacrylshikonin is a naphthoquinone derivative extracted from Lithospermum officinale^[1]. β,β-Dimethylacrylshikonin exerts anti-inflammatory, anti-tumor and antioxidant effects by inhibiting the nuclear factor κB (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways^{[2, 3]}.

In vitro, treatment of A549 cells with β,β-Dimethylacrylshikonin (15μM) for 24h induced the loss of mitochondrial membrane potential and the release of cytochrome c in the cells, and the membrane potential decreased from 81.9% to 33.2%^[4]. Treatment of human gastric cancer SGC-7901 cells with β,β-Dimethylacrylshikonin (0-15μg/mL) for 24h and 48h inhibited cell viability and induced apoptosis in a dose- and time-dependent manner, downregulated the expression of XIAP, cIAP-2 and Bcl-2, upregulated the expression of Bak and Bax, and led to loss of mitochondrial membrane potential and release of cytochrome c^[5]. Treatment of human colorectal cancer HCT-116 cells with β,β-Dimethylacrylshikonin (2.5, 5, 10μg/mL) for 12-48h inhibited cell growth in a dose- and time-dependent manner, induced apoptosis and cell cycle arrest^[6].

In vivo, intravenous injection of β,β-Dimethylacrylshikonin (0.3, 0.6, 1.2mg/kg) in HCT-116 xenograft mice significantly inhibited tumor growth, downregulated the expression of Bcl-2, and upregulated the expression of Bax in tumor tissues^[6].

References:
[1] Han J, Weng X, Bi K. Antioxidants from a Chinese medicinal herb–Lithospermum erythrorhizon[J]. Food chemistry, 2008, 106(1): 2-10.
[2] Guo C, He J, Song X, et al. Pharmacological properties and derivatives of shikonin—A review in recent years[J]. Pharmacological research, 2019, 149: 104463.
[3] Boulos J C, Rahama M, Hegazy M E F, et al. Shikonin derivatives for cancer prevention and therapy[J]. Cancer letters, 2019, 459: 248-267.
[4] Wang H, Ma X. β, β-Dimethylacrylshikonin induces mitochondria-dependent apoptosis of human lung adenocarcinoma cells in vitro via p38 pathway activation[J]. Acta Pharmacologica Sinica, 2015, 36(1): 131-138.
[5] Shen X J, Wang H B, Ma X Q, et al. β, β-Dimethylacrylshikonin induces mitochondria dependent apoptosis through ERK pathway in human gastric cancer SGC-7901 cells[J]. 2012.
[6] Fan Y, Jin S, He J, et al. Effect of β, β-dimethylacrylshikonin on inhibition of human colorectal cancer cell growth in vitro and in vivo[J]. International Journal of Molecular Sciences, 2012, 13(7): 9184-9193.

β,β-Dimethylacrylshikonin是从紫草中提取得到的一种萘醌衍生物^[1]。β,β-Dimethylacrylshikonin通过抑制核因子κB（NF-κB）和丝裂原活化蛋白激酶（MAPK）信号通路，发挥抗炎、抗肿瘤和抗氧化等作用^{[2, 3]}。

在体外，β,β-Dimethylacrylshikonin（15μM）处理A549细胞24h，诱导了细胞中线粒体膜电位的丧失和细胞色素c的释放，膜电位从81.9%降低到33.2%^[4]。β,β-Dimethylacrylshikonin（0-15μg/mL）处理人胃癌SGC-7901细胞24h和48h，以剂量和时间依赖性方式抑制了细胞活力并诱导细胞凋亡，下调了XIAP，cIAP-2和Bcl-2的表达，上调了Bak和Bax的表达，导致了线粒体膜电位丧失和细胞色素c的释放^[5]。β,β-Dimethylacrylshikonin（2.5, 5, 10μg/mL）处理人结直肠癌HCT-116细胞12-48h，以剂量和时间依赖性方式抑制了细胞生长，诱导了细胞凋亡和细胞周期停滞^[6]。

在体内，β,β-Dimethylacrylshikonin（0.3, 0.6, 1.2mg/kg）通过静脉注射治疗HCT-116异种移植小鼠，显著抑制了肿瘤的生长，下调了肿瘤组织中Bcl-2的表达，上调了Bax的表达^[6]。