Targeting non-oncogene ROS pathway by alantolactone in B cell acute lymphoblastic leukemia cells

Publication date: Available online 17 April 2019Source: Life SciencesAuthor(s): Xiaoguang Xu, Lei Huang, Zilu Zhang, Jia Tong, Jianqing Mi, Yingli Wu, Chenli Zhang, Hua YanAbstractAimsAlantolactone (ALT) is active component of natural product Inula helenium with a lot of pharmacological effects, including anti-tumor effect. The present work aimed to explore the antitumor effect of ALT in B cell acute lymphoblastic leukemia (B-ALL).Main methodsB-ALL cells were treated with various concentrations of ALT, and then trypan blue assay, Annexin V/PI staining assay, PI staining assay, western blot analysis were employed to measure the effect of ALT on viability, apoptosis and cell cycle in B-ALL cells. In addition, a synthetic bioinformatics method was used to predict the underlying mechanism of antitumor effect of ALT. Then Reactive Oxygen Species (ROS) probe Dihydroethidium (DHE) and 2′,7′-Dichlorodihydrofluorescein diacetate (DCFH-DA) were used to detect accumulation of cellular ROS. Meanwhile, DNA damage was identified by 8-oxoG, p-ATM1987, γ-H2AX and comet assay. In addition, activity of glutathione reductase (GR), thioredoxin reductase (TrxR) and catalase were measured and overexpressed in SEM and RS4;11 cells to study the inhibition on these enzymes. Finally, B-ALL NOD-SCID mouse model was used to test its performance in vivo.Key findingsALT showed good antitumor effect in B-ALL in vivo and in vitro through inducing ROS overload, which led to DNA damage. In addition, we f...
Source: Life Sciences - Category: Biology Source Type: research