Artesunate induces ROS-dependent apoptosis via a Bax-mediated intrinsic pathway in Huh-7 and Hep3B cells

Pang, Yilin; Qin, Guiqi; Wu, Liping; Wang, Xiaoping; Chen, Tongsheng

doi:10.1016/j.yexcr.2016.06.012

Cited by 42 publications

(34 citation statements)

References 62 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Abnormal cell cycle distribution can lead to decrease in proliferation, slower growth and lower survival in cancer cells 28 . To further clarify the mechanism of daphnegiravone D - induced inhibition of proliferation in Hep3B and HepG2 cells, propidium iodide (PI) staining was performed to determinate the DNA distribution 29, 30 . It was found that Hep3B and HepG2 cells were significantly arrested at G0/G1 phase after treatment with different concentrations of daphnegiravone D for 24 and 48 h (Fig.…”

Section: Resultsmentioning

confidence: 99%

A new Prenylated Flavonoid induces G0/G1 arrest and apoptosis through p38/JNK MAPK pathways in Human Hepatocellular Carcinoma cells

Wang

Sun

et al. 2017

Sci Rep

View full text Add to dashboard Cite

Prenylated flavonoids have been demonstrated to possess diverse bioactivities including antitumor effects. One new, daphnegiravone D (1), and four known (2–5) prenylated flavonoids were isolated from Daphne giraldii. Their cytotoxic activities revealed that daphnegiravone D markedly inhibited the proliferation of cancer cells, but had no apparent cytotoxicity on human normal cells. Mechanistically, daphnegiravone D induced G0/G1 arrest and apoptosis, reduced the expression of cyclin E1, CDK2 and CDK4, and promoted the cleavage of caspase 3 and PARP in Hep3B and HepG2 cells. Meanwhile, daphnegiravone D increased the level of phosphorylated p38 and attenuated phosphorylated JNK. Further studies indicated that SB203580 partially reversed daphnegiravone D-induced G0/G1 arrest and apoptosis. The addition of SP600125 to both cell lines increased the cleavage of caspase 3 and PARP, but did not affect the G0/G1 arrest. Besides, in vivo studies demonstrated that daphnegiravone D obviously inhibited tumor growth in a nude mouse xenograft model through suppressing the proliferation of tumor cells, without significant effect on body weight or pathology characteristics. Taken together, the new compound selectively inhibited the proliferation of hepatoma cells via p38 and JNK MAPK pathways, suggesting its potential as a novel natural anti-hepatocellular carcinoma agent.

show abstract

Section: Resultsmentioning

confidence: 99%

A new Prenylated Flavonoid induces G0/G1 arrest and apoptosis through p38/JNK MAPK pathways in Human Hepatocellular Carcinoma cells

Wang

Sun

et al. 2017

Sci Rep

View full text Add to dashboard Cite

show abstract

“…In addition, high ROS concentration could induce cell apoptosis and necrosis in relation with the severity and the duration of exposure [22]. Therefore, many ROS-inducing agents are currently used in clinical trials for different tumors [21, 23]. These agents could not only act as direct inhibitors of cancers, but also sensitize tumor cells to chemotherapies [24].…”

Section: Discussionmentioning

confidence: 99%

Juglone induces apoptosis of tumor stem-like cells through ROS-p38 pathway in glioblastoma

Zhang

et al. 2017

BMC Neurol

View full text Add to dashboard Cite

BackgroundJuglone is a natural pigment, which has cytotoxic effect against various human tumor cells. However, its cytotoxicity to glioma cells, especially to tumor stem-like cells (TSCs) has not been demonstrated.MethodsTSCs of glioma were enriched from U87 and two primary cells (SHG62, and SHG66) using serum-free medium supplemented with growth factors, including bFGF, EGF and B27. After treatment of juglone with gradient concentrations (0, 10, 20, and 40 μM), the viability and apoptosis of TSCs were evaluated by WST-8 assay and flow cytometry. Reactive oxygen species (ROS) was labeled by the cell-permeable fluorescent probe and detected with flow cytometry. ROS scavenger (NAC) and p38-MAPK inhibitor (SB203580) were applied to resist the cytotoxic effect. Caspase 9 cleavage and p38 phosphorylation (P-p38) were quantified by western blot. Juglone as well as temozolomide (TMZ) were administrated in intracranial xenografts and MR scan was performed every week to evaluate the anti-tumor effect in vivo.ResultsJuglone could obviously inhibit the proliferation of TSCs in glioma by decreasing cell viability (P < 0.01) and inducing apoptosis (P < 0.01), which was accompanied by increased caspase 9 cleavage in a dose-dependent manner (P < 0.01). In the meantime, juglone could generate ROS significantly and increase p38 phosphorylation (P < 0.01). In addition, pretreatment with ROS scavenger or p38-MAPK inhibitor could reverse juglone-induced cytotoxicity (P < 0.01). More importantly, juglone could also suppress tumor growth in vivo and improve the survival of U87-bearing mice compared with control (P < 0.05), although TMZ seemed to have better effect.ConclusionsJuglone could inhibit the growth of TSCs in gliomas through the activation of ROS-p38-MAPK pathway in vitro, and the anti-glioma effect was validated in vivo, which offers a potential therapeutic agent to gliomas.

show abstract

“…The mitochondria was also involved in regulating the transduction process of a wide variety of apoptotic signals [12–17]. When the mitochondria was attacked by drugs, its permeability was enhanced and membrane potential had been decreased, thus leading to endometrial swelling of mitochondrial membrane and the rapid release of cytochrome C from the mitochondria into the cytoplasm [18–20]. Furthermore, some proteins from the caspase family were activated, and the cascade reaction of cell apoptosis was induced.…”

Section: Introductionmentioning

confidence: 99%

Nanoparticle Delivery of Artesunate Enhances the Anti-tumor Efficiency by Activating Mitochondria-Mediated Cell Apoptosis

et al. 2017

Nanoscale Res Lett

View full text Add to dashboard Cite

Artemisinin and its derivatives were considered to exert a broad spectrum of anti-cancer activities, and they induced significant anti-cancer effects in tumor cells. Artemisinin and its derivatives could be absorbed quickly, and they were widely distributed, selectively killing tumor cells. Since low concentrations of artesunate primarily depended on oncosis to induce cell death in tumor cells, its anti-tumor effects were undesirable and limited. To obtain better anti-tumor effects, in this study, we took advantage of a new nanotechnology to design novel artesunate-loaded bovine serum albumin nanoparticles to achieve the mitochondrial accumulation of artesunate and induce mitochondrial-mediated apoptosis. The results showed that when compared with free artesunate’s reliance on oncotic death, artesunate-loaded bovine serum albumin nanoparticles showed higher cytotoxicity and their significant apoptotic effects were induced through the distribution of artesunate in the mitochondria. This finding indicated that artesunate-loaded bovine serum albumin nanoparticles damaged the mitochondrial integrity and activated mitochondrial-mediated cell apoptosis by upregulating apoptosis-related proteins and facilitating the rapid release of cytochrome C.

show abstract

Artesunate induces ROS-dependent apoptosis via a Bax-mediated intrinsic pathway in Huh-7 and Hep3B cells

Cited by 42 publications

References 62 publications

A new Prenylated Flavonoid induces G0/G1 arrest and apoptosis through p38/JNK MAPK pathways in Human Hepatocellular Carcinoma cells

A new Prenylated Flavonoid induces G0/G1 arrest and apoptosis through p38/JNK MAPK pathways in Human Hepatocellular Carcinoma cells

Juglone induces apoptosis of tumor stem-like cells through ROS-p38 pathway in glioblastoma

Nanoparticle Delivery of Artesunate Enhances the Anti-tumor Efficiency by Activating Mitochondria-Mediated Cell Apoptosis

Contact Info

Product

Resources

About