Laboratory of Stem Cell and Tissue Engineering, Department of Histology and Embryology, Chongqing Medical University, Chongqing 400016, China.
Department of Human Anatomy, Chongqing Medical and Health School, Chongqing 400016, China.
Chem Biol Interact. 2015 Dec 5;242:227-34. doi: 10.1016/j.cbi.2015.10.014. Epub 2015 Oct 19.
Activation and abnormal expression of histone deacetylase (HDAC) which is important target for cancer therapeutics are related to the occurrence of human leukemia. 20(s)-Ginsenoside Rh2 (20(s)-Rh2) may be a potential HDAC inhibitor (HDACi) of leukemia, but the mechanism has not been reported.
The cell proliferation and apoptosis was assessed in cultured K562 and KG-1α cells. The protein expression was measured with immunoblotting. The activities of HDAC and histone acetyltransferase (HAT) were measured with BCA. In vivo experiments were performed on naked mice carrying K562 cells for assessment of tumor growth, apoptosis, protein expression, and HDAC/HAT activities.
20(s)-Rh2 effectively induced cell cycle arrest at G0/G1 phase and apoptosis in K562 and KG1-α cells, decreased the levels of proteins associated with cell proliferation (Cyclin D1, Bcl-2, ERK, p-ERK) and activated pro-apoptotic proteins (Bax, cleaved Caspase-3, p38, p-p38, JNK, p-JNK). 20(s)-Rh2 down-regulated HDAC1, HDAC2, HDAC6, increased histone H3 acetylation and HAT activity. Moreover, 20(s)-Rh2 inhibited the growth of human leukemia xenograft tumors in vivo.
20(s)-Rh2 inhibited the proliferation of K562 and KG1-α cell by reducing the expression and activity of HDACs, increasing histone acetylation, and regulating key proteins in the downstream signaling pathways. Therefore, 20(s)-Rh2 could become a potential natural HDACi for chemotherapy of leukemia.
组蛋白去乙酰化酶（HDAC）的激活和异常表达与人类白血病的发生有关，是癌症治疗的重要靶点。20(s)-人参皂苷 Rh2（20(s)-Rh2）可能是一种潜在的白血病 HDAC 抑制剂（HDACi），但其机制尚未报道。
采用细胞增殖和凋亡实验检测 20(s)-Rh2 对 K562 和 KG-1α 细胞的作用；Western blot 检测蛋白表达；BCA 法检测 HDAC 和组蛋白乙酰转移酶（HAT）活性。裸鼠移植 K562 细胞模型，检测肿瘤生长、凋亡、蛋白表达和 HDAC/HAT 活性。
20(s)-Rh2 有效诱导 K562 和 KG1-α 细胞周期阻滞于 G0/G1 期，并诱导细胞凋亡，降低与细胞增殖相关的蛋白（Cyclin D1、Bcl-2、ERK、p-ERK）水平，激活促凋亡蛋白（Bax、cleaved Caspase-3、p38、p-p38、JNK、p-JNK）。20(s)-Rh2 下调 HDAC1、HDAC2、HDAC6，增加组蛋白 H3 乙酰化和 HAT 活性。此外，20(s)-Rh2 抑制人白血病异种移植瘤在体内的生长。
20(s)-Rh2 通过降低 HDACs 的表达和活性、增加组蛋白乙酰化以及调节下游信号通路中的关键蛋白，抑制 K562 和 KG1-α 细胞的增殖。因此，20(s)-Rh2 可能成为治疗白血病的潜在天然 HDACi。
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