The Critical Role of PTEN/PI3K/AKT Signaling Pathway in Shikonin-Induced Apoptosis and Proliferation Inhibition of Chronic Myeloid Leukemia

Cellular Physiology and Biochemistry : International Journal of Experimental Cellular Physiology, Biochemistry, and Pharmacology
Yu ChenYing Wang

Abstract

Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm. Tyrosine kinase inhibitors (TKIs) are commonly used to treat CML; however, drug resistance of CML cells to TKIs has limited their clinical application. Shikonin, a traditional Chinese herb, has long been used to treat leukemia in China, but the roles and related molecular mechanisms of shikonin treatment in CML remain unclear. Here, we aimed to evaluate the effects of shikonin on the proliferation, apoptosis, and migration of K562 cells, a CML cell line. Firstly, K562 cell proliferation and apoptosis were tested by CCK8 assay and flow cytometry with Annexin V-FITC/PI staining. Cell migration was measured by Transwell migration assay. In addition, western blot was performed to determine the proteins (PI3K, Bax, Bcl-2, cleaved caspase-3, PTEN, p-AKT, AKT, CXCR4, SDF-1, CD44) involved in the mechanism of action of shikonin. Finally, neutrophils from peripheral blood of CML patients were obtained, and cell proliferation and apoptosis were tested by CCK8 assay and flow cytometry. Shikonin reduced the proliferation of K562 cells in a time- and dose-dependent manner and promoted the apoptosis of K562 cells. Moreover, shikonin increased the PTEN level and inactivated the ...Continue Reading

Citations

Jun 7, 2019·Journal of Cellular Physiology·Chaosen YueJixiang Wu
Feb 29, 2020·Journal of Hepatocellular Carcinoma·Tong LiuChuanyong Guo
Mar 24, 2020·Journal of Enzyme Inhibition and Medicinal Chemistry·Xiao-Bao ShenXinhua Liu
Jan 10, 2019·Evidence-based Complementary and Alternative Medicine : ECAM·Meng-Yao SunQing-Feng Tang
Sep 26, 2020·Cell Death & Disease·Rui LiuYuanyan Liu
Jun 26, 2020·Frontiers in Pharmacology·Fangfang WangJinshan Tang
Sep 26, 2019·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Chuanjie GuoCheng Peng
Oct 29, 2020·BMC Complementary Medicine and Therapies·Biting WangYun Tang

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