Dihydroartemisinin upregulates death receptor 5 expression and cooperates with TRAIL to induce apoptosis in human prostate cancer cells

Abstract

Dihydroartemisinin (DHA) is a derivative of artemisinin and is an effective anti-malaria therapeutic used worldwide. In this paper, we report that DHA is as a potential anticancer drug for prostate cancer. Our data indicate that DHA suppresses the PI3-K/Akt and ERK cell survival pathways and triggers the induction of death receptor DR5 and activation of extrinsic and intrinsic cell death signaling. DHA-mediated DR5 induction appears to occur via increased transcriptional activity of DR5 promoter. Our data also show that, while DHA has strong cytotoxicity in tumor cells, it exhibits minimal cytotoxic effects on normal prostate epithelial cells. Our studies also demonstrate that DHA worked cooperatively with death ligand TRAIL. Combination of DHA and TRAIL significantly enhanced cell killing above that noted with a single agent alone. Based on these results, we propose a novel idea of developing DHA alone and/or in combination with TRAIL for the treatment of prostate cancer.

Effect of dihydroarteminin combined with siRNA targeting Notch1 on Notch1/c-Myc signaling in T-cell lymphoma cells

“…Additionally, DHA exerts an antineoplastic effect in prostate cancer cells by increasing death receptor 5 expression (24) and induces NOXA-dependent mitochondrial cell apoptosis in melanoma cells with upregulation of cellular oxidative stress (25), furthermore, DHA triggers cell cycle arrest via effects on the AKT/GSK3β/cyclin D1 pathway in A549 lung cancer cells (26). DHA could also inhibit the Wnt/β-catenin signaling pathway in lung cancer, and the expressions of key proteins including Wnt5-a/b, LRP6 and Dvl2 in the Wnt/β-catenin signaling pathway were significantly decreased (27).…”

Dihydroartemisinin induces apoptosis in skin cancer cell line A-431 via ROS pathway

“…Artemisinin and its derivatives such as Dihydroartemisinin (DHA) have been reported to induce apoptosis in pancreas, prostate, colon and neuroblastoma [8][9][10][11]. Dihydroartemisinin has been found as an antiproliferative agent in vitro and in vivo [25].…”

“…Dihydroartemisinin has been found as an antiproliferative agent in vitro and in vivo [25]. In particular, Dihydroartemisinin was considered as a potential antitumor agent in several cancer cell lines [6][7][8][9][10][11][12]. Based on these findings, we explored to determine the growth inhibitory effect of Dihydroartemisinin on the human skin cancer cells and the possible mechanism of its action was investigated.…”

“…It has been used to treat malaria and is still widely used as an effective antimalaria drug [5]. Recently, studies have suggested that artemisinin and its derivatives have anticancer properties, such as in breast, oral squamous cell carcinomas, pancreas, prostate, colon and neuroblastoma [6][7][8][9][10][11][12]. Although many studies have been performed about the underlying mechanisms of Artemisinin, the exact mechanism of this compound is still highly controversial [13,14].…”

Dihydroartemisinin suppresses glioma proliferation and invasion via inhibition of the ADAM17 pathway

“…DHA has been approved for the treatment of multidrug-resistant malaria and has an excellent safety profile [15,16]. Some laboratory studies have suggested that artemisinin derivatives, including DHA, also have significant effects against various human tumors, such as leukemia cells [17], prostate cancer [18], ovarian cells [19], pancreatic cancer [20], lung adenocarcinoma, and non-small cell lung cancer [21,22]. A previous study demonstrated that DHA could effectively inhibit U87 glioma cell proliferation, invasion, and angiogenesis [23].…”