Ze-Hong Liu1, Jing Li1, Jing Xia2, Rong Jiang1, Guo-Wei Zuo3, Xiao-Peng Li1, Yi Chen1, Wei Xiong1, Di-Long Chen4. 1. Laboratory of Stem Cell and Tissue Engineering, Department of Histology and Embryology, Chongqing Medical University, Chongqing 400016, China. 2. Department of Human Anatomy, Chongqing Medical and Health School, Chongqing 400016, China. 3. Key Laboratories of Clinical Diagnostics, Province and Ministry of Education, Chongqing Medical University, Chongqing 400016, China. 4. Laboratory of Stem Cell and Tissue Engineering, Department of Histology and Embryology, Chongqing Medical University, Chongqing 400016, China. Electronic address: xinmengyuandlc@163.com.
Abstract
BACKGROUND AND OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.
BACKGROUND AND OBJECTIVE: Activation and abnormal expression of histone deacetylase (HDAC) which is important target for cancer therapeutics are related to the occurrence of humanleukemia. 20(s)-Ginsenoside Rh2 (20(s)-Rh2) may be a potential HDAC inhibitor (HDACi) of leukemia, but the mechanism has not been reported. METHODS: 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. RESULTS: 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 humanleukemia xenograft tumors in vivo. CONCLUSION: 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.
Authors: Sang Ah Yi; Jieun Lee; Sun Kyu Park; Jeom Yong Kim; Jong Woo Park; Min Gyu Lee; Ki Hong Nam; Jee Hun Park; Hwamok Oh; Saetbyul Kim; Jihoon Han; Bo Kyung Kim; Dong-Gyu Jo; Jeung-Whan Han Journal: J Ginseng Res Date: 2018-08-08 Impact factor: 6.060