Bach1 Induces Endothelial Cell Apoptosis and Cell‐Cycle Arrest through ROS Generation

Wang, Xinhong; Liu, Junxu; Jiang, Li; Wei, Xiangxiang; Niu, Cong; Wang, Rui; Zhang, Jianyi; Meng, Dan; Yao, Kang

doi:10.1155/2016/6234043

Cited by 53 publications

(51 citation statements)

References 35 publications

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“…p53 is also a redox-regulating transcription factor via regulation of ROS production and the expression of various antioxidant enzymes (36). Increased ROS is believed to be able to activate the mitochondrial apoptotic pathway, resulting in cell death (37)(38)(39). In the present study, we found that PTE increased ROS generation both in vivo and in vitro through a p53-dependent manner.…”

Section: Discussionsupporting

confidence: 58%

Pterostilbene inhibits hepatocellular carcinoma through p53/SOD2/ROS-mediated mitochondrial apoptosis

Guo¹,

Tsuiki

Wang

et al. 2016

Oncology Reports

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Hepatocellular carcinoma (HCC) is one of the most common malignancies and the second cause of cancer-related deaths around the world. Pterostilbene (PTE), is a natural analog of resveratrol, possessing diverse pharmacological activities. In the present study, we aimed to examine the effect of PTE on tumor growth in mouse models of HCC and to elucidate the possible molecular mechanism in vivo and in vitro. We showed that PTE dose-dependently suppressed tumor growth in mice induced by diethylnitrosamine plus carbon tetrachloride, as evidenced by a decrease in the number of tumors and in the maximum size of the tumors. PTE concentration-dependently inhibited cell viability and proliferation in HepG2 cells. PTE increased caspase-3 activities and apoptosis in liver tumor tissues and cells, indicating the activation of the mitochondrial apoptotic pathway. PFTα, superoxide dismutase 2 (SOD2) lentivirus and N-acetylcysteine (NAC) significantly inhibited PTE-induced inhibition of tumor growth and cell proliferation and increase in apoptosis. PTE dose-dependently increased reactive oxygen species (ROS) levels both in liver tumor tissues and cells, which were inhibited by PFTα, SOD2 lentivirus and NAC. PTE resulted in a significant decrease in SOD2 expression in liver tumor tissues and cells, which were inhibited by PFTα, but not NAC, indicating that PTE-induced ROS generation was attributed to p53-mediated downregulation of SOD2. Collectively, PTE increased p53 expression, decreased SOD2 expression, and resulted in an increase in the ROS levels and the activation of the mitochondrial apoptotic pathway, leading to inhibition of tumor growth and cell proliferation. These data demonstrated that the p53/SOD2/ROS pathway is critical for PTE-mediated inhibition of tumor growth and HCC cell proliferation.

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Section: Discussionsupporting

confidence: 58%

Pterostilbene inhibits hepatocellular carcinoma through p53/SOD2/ROS-mediated mitochondrial apoptosis

Guo¹,

Tsuiki

Wang

et al. 2016

Oncology Reports

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“…We have shown that Bach1 binds to TCF4, reduces the interaction of β -catenin with TCF4, and disrupts Wnt/ β -catenin signaling by recruiting histone deacetylase 1 to the promoter of TCF4-targeted genes [14]. Our results also indicate that Bach1 reduces the proliferation, migration, and tube formation activity of human endothelial cells (ECs), induces endothelial cell apoptosis and cell-cycle arrest, and suppresses angiogenesis in mice with surgically induced hind-limb ischemia (HLI) [14, 15]. These observations suggest Bach1 as a major regulator of endothelial function and ischemia-induced angiogenesis.…”

Section: Introductionmentioning

confidence: 83%

“…Thus, Bach1 likely inhibits angiogenesis by regulating a variety of factors, including VEGF, IL-8, and HO-1. In addition, the results from our recent investigation suggest that higher levels (≈100-fold increase in mRNA expression) of Bach1 enhanced ROS production and induced apoptosis in ischemic mouse hindlimbs [15]. However, we found that a slight (≈2-fold) increase in Bach1b mRNA expression did not induce the apoptosis (data not shown) in zebrafish in the present study, which suggests that the effect of Bach1b overexpression on the developmental angiogenesis in zebrafish cannot be explained by apoptosis.…”

Section: Discussionmentioning

confidence: 99%

The Transcription Factor Bach1 Suppresses the Developmental Angiogenesis of Zebrafish

Jiang

Yin

et al. 2017

Oxidative Medicine and Cellular Longevity

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Bach1 disrupts Wnt/β-catenin signaling, reduces the proliferation, migration, and tube formation activity of endothelial cells (ECs), and suppresses angiogenesis in mice with surgically induced hind-limb ischemia (HLI). However, the function of Bach1 during developmental angiogenesis in zebrafish remains unclear. Here, we found that zebrafish Bach1 was expressed ubiquitously during early embryonic development in zebrafish. Bach1b mRNA injection of Tg(fli1:gfp) fish disrupted intersegmental vessels (ISV) and dorsal longitudinal anastomotic vessels (DLAV) and suppressed endogenous Wnt/β-catenin signaling and Wnt8a stimulated vascular endothelial growth factor (VEGF) and interleukin-8 (IL-8) gene expression at early embryonic stages of zebrafish. Furthermore, chromatin immunoprecipitation experiments confirmed that Bach1 occupied the TCF/LEF-binding site of the VEGF promoter in human umbilical vein endothelial cells (HUVECs). Bach1 inhibited VEGF transcription by recruiting histone deacetylase 1 (HDAC1) to the VEGF promoter in HUVECs. Exogenous administration of VEGF or IL-8 partially rescued Bach1-driven antiangiogenic functions in HUVECs. Taken together, these observations indicate that Bach1 suppresses the developmental angiogenesis of zebrafish and that this function is associated with declines in Wnt/β-catenin signaling and VEGF and IL-8 expression.

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“…It is well established that ROS, is a strong activator of AMPK, and has an important role in apoptosis [27,28,29], thus, we wondered whether ROS production is related to EPS1-1-induced AMPK activation. To evaluate the effect of EPS1-1 on ROS activity, we examined the ROS level in CT26 cells by DCF-DA staining.…”

Section: Effect Of Ros On Eps1-1-induced Ampk Activationmentioning

confidence: 99%

Exopolysaccharides isolated from Rhizopus nigricans induced colon cancer cell apoptosis in vitro and in vivo via activating the AMPK pathway

et al. 2020

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Colorectal cancer (CRC) is a leading cause of cancer-related human deaths. The exopolysaccharide (EPS1-1), isolated from Rhizopus nigricans, has been described as exhibiting anti-tumor and pro-apoptotic activity against CRC, although the underlying mechanism is poorly understood. Herein, we investigate how EPS1-1 induces apoptosis of CRC cells in vitro and in vivo. Our results show that, in vitro, EPS1-1 suppressed cell growth and facilitated apoptosis in a dose- and time-dependent manner by activating the AMP-activated protein kinase (AMPK) pathway in mouse colon cancer CT26 cells. However, treatment with small interfering RNAs (siRNAs) targeting AMPKα or with compound C, an AMPK inhibitor, interfered with the pro-apoptosis effects of EPS1-1. We also show that EPS1-1 initiated the release of reactive oxygen species (ROS) and liver kinase B1 (LKB1), both of which are necessary signals for AMPK activation. Furthermore, EPS1-1-mediated apoptosis is regulated by inactivation of mammalian target of rapamycin complex 1 (mTORC1) and activation of the jun-NH2 kinase (JNK)-p53 signaling axis dependent on AMPK activation. In vivo, azoxymethane/dextran sulfate sodium (AOM/DSS)-treated CRC mice, when administered EPS1-1, exhibited activation of the AMPK pathway, inhibition of mTORC1, and accumulation of p53 in tumor tissues. Collectively, these findings suggest that EPS1-1-induced apoptosis relies on the activation of the AMPK pathway. The present study provides evidence suggesting that EPS1-1 may be an effective target for development of novel CRC therapeutic agents.

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Bach1 Induces Endothelial Cell Apoptosis and Cell‐Cycle Arrest through ROS Generation

Cited by 53 publications

References 35 publications

Pterostilbene inhibits hepatocellular carcinoma through p53/SOD2/ROS-mediated mitochondrial apoptosis

Pterostilbene inhibits hepatocellular carcinoma through p53/SOD2/ROS-mediated mitochondrial apoptosis

The Transcription Factor Bach1 Suppresses the Developmental Angiogenesis of Zebrafish

Exopolysaccharides isolated from Rhizopus nigricans induced colon cancer cell apoptosis in vitro and in vivo via activating the AMPK pathway

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