Mitochondria-derived reactive oxygen species drive GANT61-induced mesothelioma cell apoptosis

Lim, Chuan Bian; Prêle, Cecilia M.; Baltic, Svetlana; Arthur, Peter G.; Creaney, Jenette; Watkins, D. Neil; Thompson, Philip J.; Mutsaers, Steven E.

doi:10.18632/oncotarget.2729

Cited by 25 publications

(26 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Moreover, Lim et al [42]. demonstrated that ROS accumulation played a vital role in the regulation of the Hh pathway, especially the GLI1, GLI2 expression.…”

Section: Resultsmentioning

confidence: 99%

Hypoxia Accelerates Aggressiveness of Hepatocellular Carcinoma Cells Involving Oxidative Stress, Epithelial-Mesenchymal Transition and Non-Canonical Hedgehog Signaling

Liu¹,

Tu²,

Wang³

et al. 2017

Cell Physiol Biochem

View full text Add to dashboard Cite

Background/Aims: Hypoxic microenvironment, a common feature of hepatocellular carcinoma (HCC), can induce HIF-1α expression and promote the epithelial-mesenchymal transition (EMT) and invasion of cancer cells. However, the underlying molecular mechanisms have not fully elucidated. Methods: HCC cells were cultured under controlled hypoxia conditions or normoxic conditions. Transwell assays were used to examine the migration and invasion capacity. HIF-1α siRNA, cyclopamine (a SMO antagonist) and GLI1 siRNA were used to inhibit HIF-1α transcription or Hh signaling activation. Results: In present study, we first observed a strongly positive correlation between HIF-1α and GLI1 expression in HCC tissues. Then, we showed that hypoxia significantly promoted EMT process and invasion of HCC cells, associated with activating the non-canonical Hh pathway without affecting SHH and PTCH1 expression. HIF-1α knockdown mitigated hypoxia-induced SMO and GLI1 expression, EMT invasion of HCC cells. Moreover, the SMO inhibitor or GLI1 siRNA also reversed the hypoxia-driven EMT and invasion of HCC cells under hypoxia condition. Here, we show that non-canonical Hh signaling is required as an important role to switch on hypoxia-induced EMT and invasion in HCC cells. In addition, we found that hypoxia increased ROS production and that ROS inhibitors (NAC) blocked GLI1-dependent EMT process and invasion under hypoxic conditions. To determine a major route of ROS production, we tested whether nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 4 (NOX4) is involved in hypoxia-induced ROS production. NOX4 expression was found to be increased at both mRNA and protein levels in hypoxic HCC cells. Furthermore, siRNA-mediated knockdown of NOX4 expression abolished hypoxia induced ROS generation and GLI1-dependent activation and invasion of HCC cells. Conclusion: Our findings indicate that hypoxia triggers ROS-mediated GLI1-dependent EMT progress and invasion of HCC cells through induction of NOX4 expression. Thus, hypoxia-driven ROS mediated non-canonical Hh signaling may play an important role in the initiation of EMT and provides a potential marker for cancer prevention and treatment.

show abstract

“…Moreover, Lim et al [42]. demonstrated that ROS accumulation played a vital role in the regulation of the Hh pathway, especially the GLI1, GLI2 expression.…”

Section: Resultsmentioning

confidence: 99%

Hypoxia Accelerates Aggressiveness of Hepatocellular Carcinoma Cells Involving Oxidative Stress, Epithelial-Mesenchymal Transition and Non-Canonical Hedgehog Signaling

Liu¹,

Tu²,

Wang³

et al. 2017

Cell Physiol Biochem

View full text Add to dashboard Cite

show abstract

“…The oxidative damage also leads to the release of cellular toxic proteins such as cytochrome c from the mitochondria to the cytosol, subsequently triggering apoptosis [14]. To explore whether ROS was involved in the apoptosis induced by PPV infection, we investigated the direct effect of PPV infection on the oxidative profile.…”

Section: Discussionmentioning

confidence: 99%

“…ROS, known as toxic products of cellular metabolism, are mainly produced by the mitochondria in most vertebrate cells and act as signaling molecules. Moreover, growing evidence suggests ROS are involved in regulation of many pathological processes such as cellular apoptosis [14,15]. However excessive ROS is toxic to cells, especially in the process of apoptosis.…”

Section: Introductionmentioning

confidence: 99%

Porcine parvovirus infection activates mitochondria-mediated apoptotic signaling pathway by inducing ROS accumulation

Zhao

Xiang

Bai

et al. 2016

Virol J

View full text Add to dashboard Cite

BackgroundPorcine parvovirus (PPV) infection primarily causes reproductive failure of pregnant swine and results in host cell death. Boars, as an important disseminator, shed PPV to sows via semen. PPV infects and numerously replicates in boar testicle, which results in damage of swine testicle in vivo. Reactive oxygen species (ROS), a mediator of cell apoptosis, play a crucial role in the mitochondria apoptotic pathway. However, whether PPV infection induces ST cells apoptosis and ROS accumulation is still unclear.MethodsTo determine the effects of PPV infection on the apoptosis, we detected morphological changes, DNA ladder, activities of caspases, and expression of PARP in PPV-infected ST cells. Moreover, aiming to investigate the effect of PPV infection on the mitochondrial apoptotic pathway and ROS accumulation, we detected the Δψm, apoptosis-related genes, and ROS. To investigate the role of ROS in the process of PPV-induced apoptosis, the ST cells were infected with PPV and treated with the ROS antioxidants. The ROS level was measured using Reactive Oxygen Species Assay Kit and the Δψm, expression level of Bcl-2, translocation of Bax, and redistribution of mitochondria cytochrome c were tested.ResultsIn this study, we demonstrated that PPV infection could induce apoptosis that was characterized by morphological changes, DNA fragmentation and activation of caspases. Moreover, PPV infection suppressed Bcl-2 expression, enhanced Bax expression and translocation to mitochondria, decreased the mitochondrial transmembrane potential, and triggered the release of cytochrome c, which caused the subsequent activation of caspase-9 and caspase-3 and initiation of apoptosis. However, during the process of PPV-induced apoptosis, the protein levels of Fas and FasL were not affected. Further studies showed that PPV infection caused ROS accumulation. Inhibition of ROS could reduce mitochondrial transmembrane potential and could significantly block ST cells apoptosis via suppressing Bax translocation, cytochrome c and caspase-3 activation.ConclusionsAll these results suggest that PPV-induced ROS accumulation mediates apoptosis in ST cells, which provided theoretical basis for the molecular pathogenesis of PPV infection.

show abstract

“…Treatment with resveratrol significantly suppressed colorectal cancer cell (CRC) with hepatic metastases in clinical trial (Howells et al ., ). Resveratrol inhibited proliferation of cancer cells by modulating both canonical and non‐canonical components of Wnt pathway signaling (Mazumdar et al ., , Srivastava et al ., , Lim et al ., ). Resveratrol treatment inhibited CRC invasion and hepatic metastases through down regulating MALAT1 to decrease nuclear localization of β‐catenin, thus attenuated Wnt/β‐catenin signaling (Ji et al ., ).…”

Section: Herbal Medicine Used For Clinical Hcc Treatmentmentioning

confidence: 97%

Herbal Medicine Offered as an Initiative Therapeutic Option for the Management of Hepatocellular Carcinoma

Chen

Qiu

et al. 2016

Phytother. Res.

View full text Add to dashboard Cite

Hepatocellular carcinoma (HCC) is a common malignant cancer and is the third leading cause of death worldwide. Effective treatment of this disease is limited by the complicated molecular mechanism underlying HCC pathogenesis. Thus, therapeutic options for HCC management are urgently needed. Targeting the Wnt/β-catenin, Hedgehog, Notch, and Hippo-YAP signaling pathways in cancer stem cell development has been extensively investigated as an alternative treatment. Herbal medicine has emerged as an initiative therapeutic option for HCC management because of its multi-level, multi-target, and coordinated intervention effects. In this article, we summarized the recent progress and clinical benefits of targeting the above mentioned signaling pathways and using natural products such as herbal medicine formulas to treat HCC. Proving the clinical success of herbal medicine is expected to deepen the knowledge on herbal medicine efficiency and hasten the adoption of new therapies. Copyright © 2016 John Wiley & Sons, Ltd.

show abstract

Mitochondria-derived reactive oxygen species drive GANT61-induced mesothelioma cell apoptosis

Cited by 25 publications

References 41 publications

Hypoxia Accelerates Aggressiveness of Hepatocellular Carcinoma Cells Involving Oxidative Stress, Epithelial-Mesenchymal Transition and Non-Canonical Hedgehog Signaling

Hypoxia Accelerates Aggressiveness of Hepatocellular Carcinoma Cells Involving Oxidative Stress, Epithelial-Mesenchymal Transition and Non-Canonical Hedgehog Signaling

Porcine parvovirus infection activates mitochondria-mediated apoptotic signaling pathway by inducing ROS accumulation

Herbal Medicine Offered as an Initiative Therapeutic Option for the Management of Hepatocellular Carcinoma

Contact Info

Product

Resources

About