کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2579965 | 1561599 | 2015 | 8 صفحه PDF | دانلود رایگان |
• 20(s)-Rh2 can inhibit the proliferation in K562 and KG1-α cells.
• 20(s)-Rh2 reduce the expression and activity of HDACs, increase histone acetylation.
• 20(s)-Rh2 inhibited the growth of human leukemia xenograft tumors in vivo.
• 20(s)-Rh2 is a natural histone deacetylase inhibit for chemotherapy of leukemia.
Background and objectiveActivation 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.MethodsThe 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.Results20(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.Conclusion20(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.
Journal: Chemico-Biological Interactions - Volume 242, 5 December 2015, Pages 227–234