Hu Chengjun, Xu Maozhong, Qin Rujuan, Chen Weifeng, Xu Xin
Department of Hematology, The Affiliated Jiangyin Hospital of Southeast University Medical College, Jiangyin, Jiangsu 214400, P.R. China.
Oncol Rep. 2015 Jun;33(6):3146-54. doi: 10.3892/or.2015.3896. Epub 2015 Apr 2.
Wogonin is a flavonoid isolated from Scutellaria baicalensis root and has multiple pharmacological effects, including anticancer effects. Recent studies have shown that wogonin induces cell cycle arrest and reverses multi-drug resistance in the human K562 leukemia cell line. However, its pharmacological function in the apoptosis of leukemia cells remains unknown. Therefore, we hypothesized that wogonin can induce apoptosis in the HL-60 leukemia cell line. In the present study, the HL-60 cells were treated with different doses of wogonin (0-150 µM). Wogonin inhibited the viability of HL-60 cells in a dose-dependent and time-dependent manner. Flow cytometry and analyses of caspase and PARP-1 activation and the Bax/Bcl-2 ratio, demonstrated that the cytotoxic effect of wogonin on HL-60 cells was mediated by caspase-dependent and mitochondrial-dependent apoptosis. Wogonin also induced the expression of certain members of the endoplasmic reticulum (ER) stress pathway (CHOP, GRP94 and GRP78) and the activation of multiple branches of ER stress transducers (IRE1α, PERK-eIF2α and ATF6) in the HL-60 cells. In addition, wogonin reduced the phosphorylation of PI3K and AKT in the HL-60 cells. Furthermore, constitutive activation of AKT induced by adenoviral vectors inhibited the pro-apoptotic effects and ER stress induced by wogonin in the HL-60 cells. In summary, our results indicated that wogonin induced apoptosis and ER stress in HL-60 cells, which was mediated by the inhibition of the PI3K-AKT signaling pathway.
汉黄芩素是从黄芩根中分离出的一种黄酮类化合物，具有多种药理作用，包括抗癌作用。最近的研究表明，汉黄芩素可诱导细胞周期停滞，并逆转人K562白血病细胞系中的多药耐药性。然而，其在白血病细胞凋亡中的药理功能仍不清楚。因此，我们推测汉黄芩素可诱导HL-60白血病细胞系凋亡。在本研究中，用不同剂量的汉黄芩素（0-150μM）处理HL-60细胞。汉黄芩素以剂量和时间依赖性方式抑制HL-60细胞的活力。流式细胞术以及对半胱天冬酶、PARP-1激活和Bax/Bcl-2比率的分析表明，汉黄芩素对HL-60细胞的细胞毒性作用是由半胱天冬酶依赖性和线粒体依赖性凋亡介导的。汉黄芩素还诱导HL-60细胞中内质网（ER）应激途径某些成员（CHOP、GRP94和GRP78）的表达以及ER应激转导器多个分支（IRE1α、PERK-eIF2α和ATF6）的激活。此外，汉黄芩素降低了HL-60细胞中PI3K和AKT的磷酸化。此外，腺病毒载体诱导的AKT组成型激活抑制了汉黄芩素在HL-60细胞中诱导的促凋亡作用和ER应激。总之，我们的结果表明，汉黄芩素诱导HL-60细胞凋亡和ER应激，这是由PI3K-AKT信号通路的抑制介导的。
