Dihydroartemisinin inhibits tumor growth of human osteosarcoma cells by suppressing Wnt/β-catenin signaling

Abstract

Osteosarcoma (OS) is the most common type of bone cancer. Even with early diagnosis and aggressive treatment, the prognosis for OS is poor. In the present study, we investigated the proliferation and invasion inhibitory effect of dihydroartemisinin (DHA) on human OS cells and the possible molecular mechanisms involved. We demonstrated that DHA can inhibit proliferation, decrease migration, reduce invasion and induce apoptosis in human OS cells. Using an in vivo tumor animal model, we confirmed that DHA can prevent OS formation and maintain intact bone structure in athymic mice. In addition, we examined the possible molecular mechanisms mediating the function of DHA. We found that the total protein levels and transcriptional activity of β-catenin in OS cells are reduced by DHA treatment, and this may result from the increased catalytic activity of glycogen synthase kinase 3β (GSK3β). Moreover, the inhibitory effect of DHA on OS cells is reversed by overexpression of β-catenin, but is further enhanced by knockdown of β-catenin, respectively. Collectively, our results reveal that DHA can inhibit tumor growth of OS cells by inactivating Wnt/β-catenin signaling. Therefore, DHA is a promising chemotherapy agent in the treatment of human OS.

Mechanism of dihydroartemisinin-induced apoptosis in prostate cancer PC3 cells: An iTRAQ-based proteomic analysis

“…Apoptosis induced by DHA in different cancer cells has been reported [21][22][23][24][25][26][27][28][29][30]. In the present study, we examined apoptosis in human androgen-independent PC3 prostate cancer cells after DHA treatment, by flow cytometry and TEM.…”

“…Dihydroartemisinin (DHA), a semisynthetic derivative of artemisinin isolated from the Chinese medicinal plant Artemisia annua L., has been widely used as an effective antimalarial drug [15][16][17][18][19]. Recently, many studies have shown that DHA is the most potent anticancer agent among artemisinin and its derivatives [20], and has in vitro and in vivo anticancer activity in different types of human cancer cells, such as hepatocellular carcinoma, prostate cancer, gastric cancer, osteosarcoma, breast cancer, esophageal cancer, pancreatic cancer, lung cancer, and ovarian cancer [21][22][23][24][25][26][27][28][29][30][31]. It has been demonstrated that DHA can induce apoptosis and/or inhibit proliferation of cancer cells [21][22][23][24][25][26][27][28][29][30][31].…”

Dihydroartemisinin inhibits catabolism in rat chondrocytes by activating autophagy via inhibition of the NF-κB pathway

“…The cytotoxic effects of DHA on several cancer cell types such as pancreatic cancer, glioma l and osteosarcoma have been extensively demonstrated922. However, the dose of DHA used in these studies was in excess of 1 μM, the dose used in the present study.…”

Overexpression of miR-506 suppresses proliferation and promotes apoptosis of osteosarcoma cells by targeting astrocyte elevated gene-1

“…The Wnt/β-catenin signaling pathway has been revealed to be excessively activated in osteosarcoma and contributes to the development and progression of osteosarcoma (34,35). Dihydroartemisinin inhibits tumor growth of human osteosarcoma cells by elevating the catalytic activity of glycogen synthase kinase 3β (GSK3β), which results in lower protein level and transcriptional activity of β-catenin (36). Overexpression of bone morphogenetic protein 9 decreased the expression levels of β-catenin mRNA and protein, downregulated its downstream proteins c-myc and osteoprotegerin, and suppressed the phosphorylation level of GSK-3β (Ser 9) in osteosarcoma cells (37).…”