Artesunate Induces Cell Death in Human Cancer Cells via Enhancing Lysosomal Function and Lysosomal Degradation of Ferritin

Yang, Naidi; Tan, Siew‐Ann; Ng, S. C.; Shi, Yin; Zhou, Jing; Tan, Kevin S. W.; Wong, Weng Fai; Shen, Han‐Ming

doi:10.1074/jbc.m114.564567

Cited by 142 publications

(120 citation statements)

References 68 publications

Supporting

Mentioning

115

Contrasting

Order By: Relevance

“…3I), indicating the important role of iron. In contrast, pretreatment with 50 μM DFO, a specific iron chelator [9,17], significantly prevented ARS-induced cell death (Fig. 3I), demonstrating that ARS induced iron-dependent apoptosis in HepG2 cells.…”

Section: Ars Induces Ros-independent Intrinsic Apoptosismentioning

confidence: 66%

“…A general consensus for the selective cytotoxicity of ARTs towards tumor cells is that higher concentration of intracellular iron of tumor cells makes ARTs release excess ROS to trigger proapoptotic signal pathways [4,8,14]. This hypothesis has been proved by the evidences that decreasing cellular iron by either blocking the transferrin receptors or pretreatment with DFO can markedly abrogate ARTs activity, and that preloading cancer cells with iron or iron-saturated transferrin can remarkably increase the cytotoxicity of ARTs in different cancer cell lines [17,[43][44][45][46]. However, our data that although ARS induced cellular ROS generation (Fig.…”

Section: Discussionmentioning

confidence: 91%

“…The enhanced uptake of iron by tumor cells has been proposed to accelerate cleavage of the endoperoxide bridge contained in ARTs, resulting in excess ROS products that selectively kill tumor cells [2,8]. This hypothesis was evidenced by the facts that iron addition significantly enhanced the cytotoxicity of ARTs via increasing ROS generation and treatment with iron chelator desferroxamine (DFO) rendered these compounds inactive in many cancer cell lines [15][16][17]. However, some novel ART derivatives without endoperoxide bridge also have potent anticancer effect [18,19].…”

Section: Introductionmentioning

confidence: 96%

See 2 more Smart Citations

Artesunate induces apoptosis via a ROS-independent and Bax-mediated intrinsic pathway in HepG2 cells

Qin

Liu

et al. 2015

Experimental Cell Research

View full text Add to dashboard Cite

Section: Ars Induces Ros-independent Intrinsic Apoptosismentioning

confidence: 66%

Section: Discussionmentioning

confidence: 91%

Section: Introductionmentioning

confidence: 96%

See 1 more Smart Citation

Artesunate induces apoptosis via a ROS-independent and Bax-mediated intrinsic pathway in HepG2 cells

Qin

Liu

et al. 2015

Experimental Cell Research

View full text Add to dashboard Cite

“…But under specific circumstances ferritin can behave as a pro-oxidant molecule. For example, artesunate, the anti-malarial drug with anti-tumor activity, was shown to induce cell death via enhancing lysosomal degradation of ferritin [50]. It is becoming accepted that ferritin can behave a pro-oxidant manner when certain trigger molecules can liberate the sequestered iron, or open the gated pores of ferritin [51].…”

Section: Discussionmentioning

confidence: 99%

Iron overload inhibits osteogenic commitment and differentiation of mesenchymal stem cells via the induction of ferritin

Balogh

Tolnai

Nagy

et al. 2016

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

126

View full text Add to dashboard Cite

Osteogenic differentiation of multipotent mesenchymal stem cells (MSCs) plays a crucial role in bone remodeling. Numerous studies have described the deleterious effect of iron overload on bone density and microarchitecture. Excess iron decreases osteoblast activity, leading to impaired extracellular matrix (ECM) mineralization. Additionally, iron overload facilitates osteoclast differentiation and bone resorption. These processes contribute to iron overload-associated bone loss. In this study we investigated the effect of iron on osteogenic differentiation of human bone marrow MSCs (BMSCs), the third player in bone remodeling. We induced osteogenic differentiation of BMSCs in the presence or absence of iron (0-50μmol/L) and examined ECM mineralization, Ca content of the ECM, mRNA and protein expressions of the osteogenic transcription factor runt-related transcription factor 2 (Runx2), and its targets osteocalcin (OCN) and alkaline phosphatase (ALP). Iron dose-dependently attenuated ECM mineralization and decreased the expressions of Runx2 and OCN. Iron accomplished complete inhibition of osteogenic differentiation of BMSCs at 50μmol/L concentration. We demonstrated that in response to iron BMSCs upregulated the expression of ferritin. Administration of exogenous ferritin mimicked the anti-osteogenic effect of iron, and blocked the upregulation of Runx2, OCN and ALP. Iron overload in mice was associated with elevated ferritin and decreased Runx2 mRNA levels in compact bone osteoprogenitor cells. The inhibitory effect of iron is specific toward osteogenic differentiation of MSCs as neither chondrogenesis nor adipogenesis were influenced by excess iron. We concluded that iron and ferritin specifically inhibit osteogenic commitment and differentiation of BMSCs both in vitro and in vivo.

show abstract

“…A study also identified that propranolol decreases HIF-1α, reduces downstream VEGF, VEGFR-1 and VEGFR-2 and the expression of monocyte chemoattractant protein-1, thus inhibiting angiomatous proliferation; however, there were no significant differences in the expression of matrix metalloproteinases (44). Artesunate, a compound isolated from a traditional Chinese medicine plant, is currently being evaluated for anti-tumor activity (45,46). Chinese medicine workers first identified artemisinin in the early 1970s as an effective antimalarial ingredient, extracted from sweet wormwood (Artemisia annua) (47).…”

Section: Discussionmentioning

confidence: 99%

Artesunate inhibits proliferation and invasion of mouse hemangioendothelioma cells in?vitro and of tumor growth in?vivo

et al. 2017

View full text Add to dashboard Cite

Abstract. Artesunate has been demonstrated to be a novel potential antitumor agent in numerous studies. However, its efficacy in infantile hemangioma is unknown. The aim of the present study was to investigate the role of artesunate in the control of vascular tumor biological behavior and molecular mechanism using mouse hemangioendothelioma endothelial (EOMA) cells and a nude mouse model. Cell viability, apoptosis and invasion were determined by an MTT assay, flow cytometric analysis and Transwell invasion assay, respectively. Reverse transcription-quantitative polymerase chain reaction and western blotting were utilized to examine the expression of genes and proteins. Inoculated EOMA cells were injected into the subcutaneous tissues of nude mice to observe the effect of artesunate therapy on the vascular tumor, an effect that was similar to that of pingyangmycin (PYM). It was identified that artesunate treatment (0-600 µg/ml) inhibited cell growth in a time-and dose-dependent manner. Artesunate at 300 µg/ml significantly reduced the proliferation and invasion of EOMA cells, and significantly decreased the expression of vascular endothelial growth factor (VEGF)-A, VEGFR-1, VEGFR-2 and hypoxia inducible factor-1α over time; caspase-3 was simultaneously upregulated in vitro. Artesunate significantly inhibited tumor growth, and the curative effect was similar to that observed with PYM in vivo. It was concluded that artesunate could effectively inhibit the growth of vascular tumors, and thus could be a novel drug candidate for the treatment of infantile hemangioma.

show abstract

Artesunate Induces Cell Death in Human Cancer Cells via Enhancing Lysosomal Function and Lysosomal Degradation of Ferritin

Cited by 142 publications

References 68 publications

Artesunate induces apoptosis via a ROS-independent and Bax-mediated intrinsic pathway in HepG2 cells

Artesunate induces apoptosis via a ROS-independent and Bax-mediated intrinsic pathway in HepG2 cells

Iron overload inhibits osteogenic commitment and differentiation of mesenchymal stem cells via the induction of ferritin

Artesunate inhibits proliferation and invasion of mouse hemangioendothelioma cells in?vitro and of tumor growth in?vivo

Contact Info

Product

Resources

About